psychotropic
psychosis

 Author:
            Riederer, P.; Lange, K. W.; Kornhuber, J.; Danielczyk, W.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 42, 22, 1992, 265-268
 Title:
            Glutamatergic-Dopaminergic Balance in the Brain Its importance in
            motor disorders and schizophrenia
 Abstract:
            Dopamine appears to be of less importance in the regulation of
            psychomotor functions than was previously thought.A central
            dopaminergic-glutamatergic balance may be important for both
            akinetic motor disorders and psychosis.In Parkinson's disease
            glutamate antagonists may counteract central glutamatergic
            hyperactivity and may be of value as anti-parkinsonian drugs.An
            increase of dopaminergic activity and/or a reduction of glutamatergic
            activity may contribute to the development of paranoid hallucinatory
            psychosis in schizophrenic patients and of pharmacotoxic psychosis in
            Parkinson's disease.Because of possibly severe side-effects of
            glutamatergic antagonists and agonists in the treatment of akinesia
            and psychosis, the development of partial glutamate
            agonists/antagonists could be an alternative strategy capable of
            producing antipsychotic or anti-kinetic effects with only mild adverse
            reaction. Key words: Brain, chemical information transmission,
            glutamatergic-dopaminergic
            balance.Dopamine.Glutamate.Parkinson's disease.Psychosis,
            pharmacotoxic.Schizophrenia
 CNR:
            5648251


 Author:
            Yevich, Joseph P.; New, James S.; Lobeck, Walter G.; Dextraze,
            Pierre; Brenstein, Edith; et al.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 35, 24, 1992, 4516-4525
 Title:
            Synthesis and Biological Characterization of
            a-(4-Fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazinebutanol and
            Analogues as Potential Atypical Antipsychotic Agents
 Abstract:
            A series of 1-(pyrimidin-2-yl)piperazine derivatives were prepared and
            evaluated in receptor binding assays and in in vivo behavioral
            paradigms as potential atypical antipsychotic agents.Compound 16
            (BMS 181100 (formerly BMY 14802)) emerged as the lead compound
            from within the series on the basis of its good activity and duration of
            action in the inhibition of both conditioned avoidance responding and
            apomorphine-induced stereotopy in the rat.Compound 16 not only
            failed to induce catalepsy in the rat but was quite effective in reversing
            the cataleptic effect of neurolepti c agents, thus indicating a low
            propensity for causing extrapyramidal side effects.In comparison to
            reference antipsychotic agents, 16 appeared to be less sedating and
            was relatively weaker in causing muscle incoordination.The
            compound was essentially inactive in binding to dopamine D2
            receptors and its chronic administration to rats did not result in
            dopamine receptor supersensitivity.It exhibited modest to weak affinity
            for 5-HT1A and a1 receptors but was found to be a fairly potent ligand
            for s binding sites (IC50 vs (+)-<3H>-3-PPP = 112 nM).Although the
            resolved enantiomers of racemic 16 did not show dramatic differences
            from racemate or from each other in most tests, the R(+) enantiomer
            was up to 11-fold more potent than its antipode in binding to s
            sites.Several studies have indicated that 16 may be a limbic-selective
            agent which may modulate dopaminergic activity by an indirect
            mechanism.The compound has been selected for clinical evaluation in
            the treatment of psychosis.
 CNR:
            5712273

 Author:
            Russell, Michael G. N.; Baker, Raymond; Billington, David C.; Knight,
            Antony K.; Middlemiss, Derek N.; Noble, Alison J.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 35, 11, 1992, 2025-2033
 Title:
            Benz<f>isoquinoline Analogues as High-Affinity s Ligands
 Abstract:
            This paper describes the synthesis of some conformationally restricted
            4-phenylpiperidine analogues and their affinities for the guinea pig
            cerebellum s recognition site (<3H>-DTG) and the rat striatum
            dopamine D2 receptor (<3H>-(-)-sulpiride) in order to develop potent
            selective s ligands as tools in the investigation of this site in
            psychosis.It was found that both hexa- and octahydrobenz<f>
            isoquinolines with lipophilic N-substituents had high affinities for the s
            site.Notably,
            trans-3-cyclohexyl-1,2,3,4,4a,5,6,10b-octahydrobenz<f>isoquinoline
            (26) had anaffinity of 0.25 nM making it the highest affinity s ligand
            reported to date.Moreover, it is at least 10000-fold selective over the D2
            receptor and could prove to be a valuable tool in the study of s
            sites.Other analogues such as 1H-indeno<2,1-c>pyridines and
            1H-benzo<3,4>cyclohepta<1,2-c>pyridines also displayed high s site
            affinity.
 CNR:
            5854565


 Author:
            New, James S.; Yevich, Joseph P.; Temple, Davis L.; New, Kimberly
            B.; Gross, Sharon M.; et al.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 31, 3, 1988, 618-624
 Title:
            Atypical Antipsychotic Agents: Patterns of Activity in a Series of
            3-Substituted 2-Pyridinyl-1-piperazine Derivatives
 Abstract:
            A series of 3-substituted 2-pyridinyl-1-piperazine derivaties have been
            appended to cyclic imide groups and evaluated for their potential
            antipsochotic activity.The dopamine receptor affinities of these target
            molecules, as well as their ability to block apomorphine-induced
            stereotypy or reverse neuroleptic-induced catalepsy, was dependent
            on the lipophilic and electronic characteristics of the substituent
            situated on the pyridine ring.Groups with +s and -p values were most
            consistent with the desired biological profile of the target molecules,
            the cyano moiety being the optimum choice.Evaluation of compound
            12 in a monkey model of amphetamine psychosis, and the regional
            selectivity it expresses for the A10 dopaminergic cell bodies in
            electrophysiological experiments, suggest this compound would be an
            atypical antipsychotic agent with few side effects.
 CNR:
            5837720


 Author:
            Agarwal, D. P.; Hoo, J. J.; Tjaden, A.; Nishigaki, I.; Beckermann, W. J.;
            et al.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 35, 11, 1985, 1639-1642
 Title:
            Effect of Amphetamine on Brain Catecholamines, Brain b-Endorphin,
            Serum Prolactin, Catechol-O-methyltransferase and Monoamine
            Oxidase of Various Organs in the Rat
 Abstract:
            Rats were treated with amphetamine to induce an amphetamine
            psychosis which resembles paranoid schizophrenia.Brain
            catecholamines, brain b-endophrin, serum prolactin as well as
            catechol-O-methyltransferase and monoamine oxidase were
            subsequently measured.The norepinephrine levels were significantly
            lower in brain regions of rats treated with amphetamine whereas levels
            of dopamine and b-endorphin remained the same.No significant
            changes were found in the levels of catechol-O-methyltransferase,
            monoamine oxidase and serum prolactin.In view of recent findings by
            other investigators in this field, our results suggest an important role of
            the adrenergic system in the pathogenesis of amphetamine psychosis.
            - Key words: Amphetamine, pharmacology; b-Endorphin;
            Catecholamines; Catechol-O-methyltransferase; Monoamine oxidase;
            Prolactin
 CNR:
            5833843

 Author:
            Diouf, O.; Depreux, P.; Lesieur, D.; Poupaert, J. H.; Caignard, D. H.
 Reference:
            Journal, EJMCA5, Eur.J.Med.Chem.Chim.Ther., EN, 30, 9, 1995,
            715-720
 Title:
            Synthesis and evaluation of new 2-piperazinylbenzothiazoles with high
            5-HT1A and 5-HT3 affinities
 Abstract:
            Original 2-piperazinylbenzothiazole derivatives were synthesized and
            studied as mixed ligands for serotoninergic 5-HT1A and 5-HT3
            receptors.The studied compounds exhibited significant affinities for
            these two serotoninergic receptor subtypes.The pharmacological
            profile of these ligands was agonist for 5-HT1A receptors and
            antagonist for 5-HT3 receptor subsites.Compounds with such a
            pharmacological profile are of clinical relevance in the treatment of
            psychotropic diseases (eg, anxiety, depression and
            schizophrenia).The present paper reports the chemistry and the in vitro
            pharmacological evaluation of these ligands. benzothiazole /
            benzothiazolin-2-one / serotonin / 5-HT1A receptor / 5-HT3 receptor /
            psychotropic disease
 CNR:
            6000989

 Author:
            Forfar, I.; Jarry, C.; Quermonne, M. A.; Boulouard, M.
 Reference:
            Journal, EJMCA5, Eur.J.Med.Chem.Chim.Ther., EN, 29, 10, 1994,
            761-766
 Title:
            Synthesis and psychotrope evaluation of new 3-ureidopropan-2-ols
            using the skin conductance reaction (SCR)-habituation test
 Abstract:
            The syntheses of 1-substituted 3-ureidopropan-2-ols 2 and
            3-acetyl-5-(1-phenyl-4-piperazinyl)methyl-2-oxazolidinones 5 from the
            corresponding 2-amino-2-oxazolines 1 are described.Some of these
            compounds have been investigated for psychotropic activity in mice
            using the skin conductance reaction (SCR)-habituation test.All the
            compounds produced a delay in habituation.The standard delaying
            dose (SDD 150) that delays SCR extinction until 150 100ths of an hour
            (+50percent control time) was compared with that of the reference drug
            fenozolone for all the compounds.Keywords: 3-ureidopropan-2-ol /
            2,3-diacetyl-2-iminooxazolidine / 3-acetyl-2-oxazolidinone / skin
            conductance reaction (SCR)-habituation test / stimulant activity
 CNR:
            5948065

 Author:
            Khokhlova, L. N.; Germane, S.; Erchak, N. P.; Lukevits, E.
 Reference:
            Journal, CHCCAL, Chem.Heterocycl.Compd.(Engl.Transl.), EN, 30, 3,
            1994, 279-282
 Title:
            SYNTHESIS AND PSYCHOTROPIC PROPERTIES OF
            BIS(2-THENYLIDENE)DIAMINES AND THEIR SILYL DERIVATIVES
 Abstract:
            The condensation of diamines with the corresponding aldehydes gave
            bis(2-thenylidene)diamines and their silyl derivatives.The structure of
            the compounds has been confirmed by their PMR spectra.It has been
            shown that the introduction of the trimethylsilyl group increases the
            toxicity, prolongs the hexenal narcosis and the antihypoxy activity, has
            a positive effect on the memory processes, and has no influence on
            the coordination of movements, the muscle tone, and the body
            temperature.All compounds possess an antialcohol activity, whereby
            the silyl derivatives have the stronger one.
 CNR:
            5959037

 Author:
            Guryn, Roman; Szadowska, Anna; Pakulska, Wanda
 Reference:
            Journal, APPHAX, Acta Pol.Pharm., EN, 51, 6, 1994, 483-488
 Title:
            DIAZEPINOQUINAZOLINES PART II. SYNTHESIS AND
            PHARMACOLOGICAL ACTIVITY OF SOME DERIVATIVES OF
            1,4-DIAZEPINO<2,1-b>QUINAZOLINE
 Abstract:
            New derivatives of 1,4-diazepino<2,1-b>quinazoline were
            obtained.The diazepino quinazoline <IV> was obtained by the
            condensation of
            2,5,6,7-tetrahydro-3-(methylthio)-1-phenyl-1H-1,4-diazepine with
            5-chloroantranilic acid.Compounds was prepared in two steps from
            2,3,4,5-tetrahydro-1,4-diazepino<2,1-b>quinazolin-7(1H)-one.The
            derivatives <II-IV>, <VII>, <VIII> were screened for their psychotropic
            activity.Keywords: 1,4-diazepino<2,1-b>quinazolin derivatives,
            synthesis, psychotropic activity
 CNR:
            5960884

 Author:
            Paronikyan, E. G.; Sirakanyan, S. N.; Noravyan, A. S.; Arzanunts, E. M.; Paronikyan, R. G.; et al.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 28, 1, 1994, 25-28
 Title:
            SYNTHESIS OF
            8-BENZYLAMINO-1,2-DIHYDRO-10-OXO-2,2,5-TRIMETHYL-4H-PYRANO<4'3':4,5>PYRIDO<3,2-e>-1,3-THIAZINE
            AND ITS PSYCHOTROPIC ACTIVITY
 Abstract:
 CNR:
            5960905

 Author:
            Liegeois, Jean-Francois F.; Bruhwyler, Jacques; Damas, Jacques; Nguyen,
            Thuy Phuong; Chleide, Eric M. G.; et al.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 36, 15, 1993, 2107-2114
 Title:
            New Pyridobenzodiazepine Derivatives as Potential Antipsychotics:
            Synthesis and Neurochemical Study
 Abstract:
            The discovery of a new, safe, atypical antipsychotic remains an important
            challenge. To achieve this goal, a series of
            N-methylpiperazinopyrido<2,3-b><1,4>- and -<1,5>- and
            -pyrido<4,3-b><1,4>- and -<1,5>-benzodiazepines were synthesized. The
            dopaminergic (D1, D2), serotonergic (5-HT2), and cholinergic (M) affinities,
            frequently remarked in the action mechanisms of antipsychotic drugs, were
            determined using their respective in vitro receptor binding assays. All
            affinities were reduced for each compound. Optimal substituents were found
            to be in the 2- or 8-position for the retention of affinities, while substitution at
            the 5-position by acyl or alkyl groups dramatically diminished binding
            affinities. Pyridobenzodiazepine derivatives, such as clozapine, were found
            to be inactive or only weakly effective against apomorphine-mediated
            stereotypes in rats. In an original and complex behavioral model developed
            in dogs and successfully used to differentiate distinct classes of psychotropic
            drugs and to discriminate between typical and atypical neuroleptic drugs,
            8-chloro-6-(4-methyl-1-piperazinyl)-11H-pyrido<2,3-b><1,4>benzodiazepine
            (9),
            8-methyl-6-(4-methyl-1-piperazinyl)-11H-pyrido<2,3-b><1,4>benzodiazepine
            (12), and 5-(4-methyl-1-piperazinyl)-11H-pyrido<2,3-b><1,5>benzodiazepine
            (16) showed most of the behavioral characteristics previously described for
            neuroleptics. Their neurochemical profiles, particularly their 5-HT2/D2 pKi
            ratios, were compatible with an atypical antipsychotic effect. These
            compounds were selected for further investigation. The proposed
            modulations could lead to new possibilities for the pharmacochemistry of
            diarylazepines.
 CNR:
            5814438

 Author:
            Shen, Meng-Ru; Yang, Rei-Cheng; Chen, Shun-Sheng
 Reference:
            Journal, JPPMAB, J.Pharm.Pharmacol., EN, 44, 6, 1992, 534-536
 Title:
            Effects of lithium and haloperidol on human sperm motility in-vitro
 Abstract:
            Two psychotropic drugs, lithium and haloperidol, were evaluated for
            their in-vitro effects on sperm motility using a transmembrane
            migration method.Sperm motility was measured either immediately
            after semen had been mixed with the drug or after a 2 h incubation
            period at 37 deg C.Lithium inhibited human sperm motility in a
            dose-dependent manner with an EC50 of 10 mM when the
            semen-lithium mixture had been incubated.Sperm motility was
            increased to 127percent of control when semen had been incubated
            with 0.027 mM haloperidol; this concentration was within the
            therapeutic range.
 CNR:
            5657688

 Author:
            Stefancich, Giorgio; Artico, Marino; Silvestri, Romano; Pantaleoni, Gian Carlo; Giorgi, Raffaele; Palumbo, Giancarlo
 Reference:
            Journal, FRMCE8, Farmaco, EN, 47, 7/8, 1992, 987-999
 Title:
            RESEARCHES ON PSYCHOTROPIC AGENTS. IV. SYNTHESIS AND NEUROPSYCHOPHARMACOLOGICAL
            EFFECTS OF
            1,3,4,14b-TETRAHYDRO-10-METHYL-2H,10H-PYRAZINO<2,1-d>PYRROLO<1,2-b><1,2,5>BENZOTRIAZEPINE
            AND ITS DERIVATIVES
 Abstract:
            The synthesis and neuropsychopharmacological properties of new
            1,3,4,14b-tetrahydro-2H,10H-pyrazino<2,1-d>pyrrolo<1,2-b><1,2,5>benzotriazepine derivatives related to
            antidepressant agent aptazepine are reported.The new derivatives displayed sedative-miorelaxant activity in mice,
            but no significant antagonist effect on clonidine blocade of phenylquinone-induced abdominal constriction.Among
            test compounds 4a, 4l and 4n showed high antinociceptive effect on the hot-plate test and compound 4e protected
            from death and convulsion all the electroshocked animals.
 CNR:
            5705401

 Author:
            Brel', A. K.; Petrov, V. I.; Ozerov, A. A.; Gunger, A. A.; Sazhin, V. A.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 26, 9-10, 1992,
            772-774
 Title:
            SYNTHESIS AND STUDY OF THE TOXIC AND PSYCHOTROPIC
            PROPERTIES OF 3-DIALKOXYPHOSPHORYLPROPYLGLYCIDYL
            ETHERS
 Abstract:
 CNR:
            5813581

 Author:
            Roig, M. G.; Bello, F.; Burguillo, F. J.; Cachaza, J. M.; Kennedy, J. F.
 Reference:
            Journal, JPMSAE, J.Pharm.Sci., EN, 80, 3, 1991, 267-270
 Title:
            In Vitro Interaction between Psychotropic Drugs and Alcohol
            Dehydrogenase Activity
 Abstract:
            A series of CNS-stimulating and-depressant drugs have been studied
            for their in vitro interaction with horse liver alcohol dehydrogenase
            (ADH) activity.The depressant drugs studied included barbital,
            phenobarbital, thiopental, nitrazepam, chlorpromazine, sulpiride,
            clomethiazole, Li2CO3, diazepam, phenytoin, ethosuximide,
            morphine, and codeine.The stimulant drugs were theopylline, caffeine,
            amphetamine, imipramine, chlorimipramine, amitriptyline, and
            tranylcypromine.The results were as follows.First, ADH activity was
            inhibited by the action of chlorpromazine, tranylcypromine, imipramine,
            chlorimipramine, amitriptyline, sulpiride, amphetamine, codeine,
            ethosuximide, morphine, clomethiazole, nitrazepam, Li2CO3,
            theophylline, and phenobarbital, in descending order of inhibitory
            effect.Second, inhibition followed by activation of ADH activity was
            observed for imipramine and chlorimipramine.Third, activation of ADH
            activity was observed for phenytoin.Finally, the following drugs were
            not seen to exert any effect on ADH activity: barbital, thiopental,
            diazepam, and caffeine.
 CNR:
            5525631

 Author:
            Petit, S; Nallet, JP; Guillard, M; Dreux, J; Chermat, R; et al.
 Reference:
            Journal, EJMCA5, Eur.J.Med.Chem.Chim.Ther., FR, 26, 1, 1991,
            19-32
 Title:
            Syntheses et activites psychotropes de 3,4-diarylpiperidines.
            Correlation structure-activite et recherche d'une activite
            antihypertensive
 Abstract:
            Interesting psychotropic properties (psychostimulant, anti-depressant)
            were shown for a series of 3,4-diarylpiperidines.Optimization of these
            properties was obtained by Topliss method for determining the
            structure-activity relationship.Anti-depressant activity with little
            psychostimulant effect was observed in Mice and Rats with the trans
            4-(4-trifluoromethylphenyl)-3-phenyl piperidine.Antihypertensive
            activity was not found among dopamine chained
            piperidines.Synthesis, relative configuration and conformation,
            pharmacologic study of 3,4-diarylpiperidines are described.
 CNR:
            5536288

 Author:
            Markosyan, A. I.; Oganisyan, M. G.; Kuroyan, R. A.; Sukasyan, R. S.; Arzanunts, E.
            M.; Sarkisyan, I S.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 25, 8, 1991, 536-539
 Title:
            SYNTHESIS AND PSYCHOTROPIC PROPERTIES OF
            4-AMINO-3-CYANO-1,2-DIHYDROSPIRO(NAPHTHALENE-2,1'-CYCLOPENTANE)
            DERIVATIVES
 Abstract:
 CNR:
            5645255


 Author:
            Stefancich, G.; Artico, M.; Silvestri, R.; Pantaleoni, G. C.; Giorgi, R.;
            Palumbo, G.
 Reference:
            Journal, FRMCE8, Farmaco, EN, 45, 1, 1990, 7-27
 Title:
            RESEARCH ON PSYCHOTROPIC AGENTS. III. ANTIDEPRESSANT
            ACTIVITY AND NEUROPSYCHOBEHAVIOURAL EFFECTS OF NEW
            5H-PYRROLO<1,2-b><1,2,5>BENZOTRIAZEPINE DERIVATIVES
 Abstract:
            The synthesis of 5H-pyrrolo<1,2-b><1,2,5>benzotriazepine derivatives
            related to imipramine and aptazepine antidepressant agents is
            reported.Pharmacological screening on new tricyclic derivatives
            showed that in some cases antidepressant effects at equimolecular
            dose with imipramine are associated with sedative-muscle relaxant
            activities and antinociception.
 CNR:
            5503600

 Author:
            Valenta, Vladimir; Vlkova, Marie; Holubek, Jiri; Svatek, Emil; Metysova,
            Jirina; Protiva, Miroslav
 Reference:
            Journal, CCCCAK, Collect.Czech.Chem.Commun., EN, 55, 3, 1990,
            797-808
 Title:
            POTENTIAL NEUROLEPTICS OF THE ORTHOPRAMIDE SERIES;
            SYNTHESIS OF
            N-(3-(TERT.AMINO)PROPYL)-5-SULFAMOYL-2-METHOXYBENZAMIDES
 Abstract:
            Heating ethyl 5-sulfamoyl-2-methoxybenzoate with a series of twelve
            3-(tert.amino)propylamines (IIIa-IIIl) afforded the title compounds IIa-IIl which
            were transformed to salts and subjected to pharmacological screening as
            potential neuroleptics of the sulpiride series.Only compounds IId (hydrogen
            oxalate, VUFB-15 453) and IIg (methanesulfonate, VUFB-15 397) showed
            indications of the desired psychotropic activity.
 CNR:
            5509991

 Author:
            Nacci, Vito; Fioroni, Isabella; Garofalo, Antonio; Cagnotto, Alfredo
 Reference:
            Journal, FRMCE8, Farmaco, EN, 45, 5, 1990, 545-558
 Title:
            RESEARCH ON COMPOUNDS WITH PSYCHOTROPIC ACTIVITY IX - Synthesis
            of 6-p-methoxyphenylpyrrolo<2,1-d><1,5>benzothiazepines and evaluation of their
            affinities for BDZ and GABA receptor subtypes.
 Abstract:
            6-p-Methoxyphenylpyrrolo<2,1-d><1,5>benzothiazepin-7(6H)-one (IV),
            cis-7-acetoxy-6,7-dihydro-6-p-methoxyphenylpyrrolo<2,1-d><1,5>benzothiazepine
            (V) and some significant
            7-acyloxy-6-p-methoxyphenylpyrrolo<2,1-d><1,5>benzothiazepines (VI a-g) were
            synthesized and tested in vitro for inhibition of the specific binding of
            3H-Flunitrazepam, 3H-PK 11195, 3H-Muscimol and 3H-(-)Baclofen to central and
            peripheral benzodiazepine, GABA-A and GABA-B receptors, respectively.The
            compounds (IV), (VI a) and (VI c) were active on the peripheral benzodiazepine
            receptor; in particular (VI a) and (VI c) were very active.The compound (VI g)
            showed an affinity, even though scanty, for the central benzodiazepine receptor.
 CNR:
            5513763

 Author:
            Petit, S.; Nallet, J. P.; Guillard, M.; Dreux, J.; Chermat, R.; et al.
 Reference:
            Journal, EJMCA5, Eur.J.Med.Chem.Chim.Ther., FR, 25, 8, 1990,
            641-652
 Title:
            Synthesis and psychotropic activity of 3,4-diarylpiperidin-2-ones:
            structure-activity relationship
 Abstract:
            Interesting psychotropic properties (psychostimulant, anti-depressant)
            were shown for a series of 3,4-diarylpiperidin-2-ones.Optimization of
            these properties was obtained by the Topliss method for determining
            the structure-activity relationship.Anti-depressant activity with little
            psychostimulant effect was observed in mice and rats in the case of
            4-(4-chloro-3-trifluoromethylphenyl)-3-phenylpiperidin-2-one
            trans.Synthesis of piperidin-2-one and a pharmacologic study are
            described; the relative configuration and conformation of these
            compounds were determined.
 CNR:
            5518349

 Author:
            Mouysset, G.; Payard, M.; Couquelet, J.; Bastide, P.; Stenger, A.; et al.
 Reference:
            Journal, FRMCE8, Farmaco, EN, 45, 8, 1990, 847-857
 Title:
            SYNTHESIS AND PHARMACOLOGICAL STUDY OF NEW
            N-METHYL 1,2,3-TRIAZOLE DERIVATIVES OF 2-CYANO
            CHROMONES
 Abstract:
            The reaction of various 2-cyano chromones with diazomethane
            generated a series of 21 N-methyl triazoles, with a benzopyrone moiety
            and divided into three isomeric groups.The anti-inflammatory,
            psychotropic and anti-allergic effects of these new compounds were
            evaluated.The results obtained did not confirm their expected
            potentialities.
 CNR:
            5522685

 Author:
            Azafonov, N. E.; Sedishev, I. P.; Zhulin, V. M.
 Reference:
            Journal, BACCAT, Bull.Acad.Sci.USSR Div.Chem.Sci.(Engl.Transl.),
            EN, 39, 4.1, 1990, 738-741
 Title:
            HENRY CONDENSATION AT HIGH PRESSURES. 1. SYNTHESIS
            OF 1-(3,4-METHYLENEDIOXYPHENYL)-2-NITRO-1-BUTENE AND
            AN IMPROVED SYNTHESIS OF
            1-(3,4-METHYLENEDIOXYPHENYL)-2-METHYLAMINOBUTANE
 Abstract:
            The hitherto inaccessible nitroolefin (VII), which is the most convenient
            intermediate for the synthesis of the psychotropic amine (VIII), has
            been obtained by the direct condensation at high pressures (up to
            1500 MPa) of piperonal (V) with 1-nitropropane (VI).The structure of
            (VII) was confirmed by direct synthesis from pyrocatechol (X).The
            amine (VIII) was obtained in three steps from (VII).This synthesis of
            (VIII) is shorter than that previously reported.
 CNR:
            5533347

 Author:
            Kovalev, G. V.; Rakhimov, A. I.; Sazhin, V. A.; Ozerov, A. A.;
            Zharkovskii, A. M.; et al.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 24, 5, 1990,
            331-334
 Title:
            N-ACYL DERIVATIVES OF D,L-ASPARTIC ACID: SYNTHESIS,
            PSYCHOTROPIC PROPERTIES, AND EFECT ON BINDING OF
            3H-GLUTAMATE TO BRAIN MEMBRANES
 Abstract:
 CNR:
            5535930

 Author:
            Kitova, I. I.; Raevskii, O. A.; Sapegin, A. M.; Andronati, S. A.;
            Prokopenko, I. A.; et al.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 24, 5, 1990,
            365-366
 Title:
            SYNTHESIS OF TWO PSYCHOTROPIC COMPOUNDS OF THE
            1,4-BENZODIAZEPINE SERIES
 Abstract:
 CNR:
            5535952

 Author:
            Tolstikova, T. G.; Davydova, V. A.; Shul'ts, E. E.; Vafina, G. F.;
            Safarova, G. M.; et al.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 24, 7, 1990,
            465-469
 Title:
            SYNTHESIS AND PSYCHOTROPIC PROPERTIES OF DIHYDRO-,
            TETRAHYDRONAPHTHO-, AND ANTHRAQUINONES, CONTAINING
            A HETEROCYCLIC FRAGMENT
 Abstract:
 CNR:
            5579774

 Author:
            Zhdanov, Yu. A.; Vedernikova, I. V.; Simkina, Yu. N.; Ryabukhin, Yu. I.;
            Khaitin, M. I.; et al.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 23, 5, 1989, 378-383
 Title:
            SYNTHESIS AND PSYCHOTROPIC ACTIVITY OF
            4-OXO-1-<HYDROXY(ACETOXY)PHENYL>-1,4-DIHYDROPYRIMIDINES
 Abstract:
 CNR:
            5510624

 Author:
            Moussavi, Z.; Bonte, J. P.; Lesieur, D.; Leinot, M.; Lamar, J. C.; et al.
 Reference:
            Journal, FRMCE8, Farmaco, FR, 44, 1, 1989, 77-88
 Title:
            (ARYLPIPERAZINO-4 BUTYRYL)-6 BENZOXAZOLINONES ET
            PRODUITS DE REACTION: ETUDE CHIMIQUE ET
            PHARMACODYNAMIQUE
 Abstract:
            The synthesis of various
            6-(4-arylpiperazino-butyryl)-3-methylbenzoxazolines and their
            reduction products,
            6-(4-arylpiperazino-1-hydroxybutyl)-3-methyl-benzoxazolines and
            6-(4-arylpiperazino-butyl)-3 methyl-benzoxazolines, is described.These
            compounds were tested for psychotropic and analgesic activities.
 CNR:
            5863732

 Author:
            Voronina, T. A.; Karaseva, T. L.; Golovenko, N. Ya.; Rokachinskaya, M.
            G.; Basok, S. S.; et al.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 22, 6, 1988,
            444-447
 Title:
            PSYCHOTROPIC PROPERTIES OF AZA-15-CROWN-5
            DERIVATIVES WITH PHARMACOPHORIC GROUPS
 Abstract:
 CNR:
            5703490

 Author:
            Morozov, I. S.; Anisimova, V. A.; Avdyunina, N. I.; Lukova, O. A.; Pyatin,
            B. M.; et al.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 22, 7, 1988,
            539-543
 Title:
            SYNTHESIS AND NEURO-PSYCHOTROPIC ACTIVITY OF
            ADAMANTYLIMIDAZO<1,2-a>BENZIMIDAZOLES
 Abstract:
 CNR:
            5749303

 Author:
            Al-Rashood, Khalid A.; Mustafa, Ali A.; Alhaider, Abdulqader A.;
            Giwanim Omer T.; Madani, Abdul Azim E.; El-Obeid, Humeida A.
 Reference:
            Journal, JPMSAE, J.Pharm.Sci., EN, 77, 10, 1988, 898-901
 Title:
            Antipsichotic Properties of New N-(4-Substituted-1-Piperazinylethyl)-
            and N-(4-Substituted-1-Piperidinylethyl)-Phthalimides
 Abstract:
            A series of N-(4-phenyl- and 4-pyridyl-1-piperazinylethyl)- and
            N-(4-phenyl-1-piperidinylethyl)-phthalimides were synthesized and
            tested for antipsychotic activity.All compounds supressed the
            spontaneous motor activity and the apomorphine-induced climbing in
            mice and pergoline-induced locomotor activity in rats, demonstrating
            psychotropic properties equal to the corresponding properties of
            sulpiride.Although the compounds, like sulpiride, were less potent than
            haloperidol in blocking the locomotor activities, they caused no
            catalepsy, a major side effect following treatment with conventional
            antipsychotic agents.It is likely that the new compounds produce their
            neuroleptic activities through inhibition of limbic dopamine receptors.
 CNR:
            5836920

 Author:
            Ahmad, Ishtiaq
 Reference:
            Journal, JICSAH, J.Indian Chem.Soc., EN, 65, 1988, 362-364
 Title:
            Some Newer Quinazolones as Psychotropic Agents
 Abstract:
            Some substituted-quinazolones have been synthesised with a view to
            evaluate CNS activity.The psyhopharmacological sreening has shown
            to possess anticonvulsant activity, observed against
            penlylenetetrazole.In vivo MAO inhibitory effect of these compounds
            were studied during oxidative deaminisation of benzylamine using rat
            brain homogenate.
 CNR:
            5865032

 Author:
            Matsuo, N.; Yamada, K.; Kumagai, M.; Nagashima, M.; Matsumoto, S.;
            et al.
 Reference:
            Journal, JPPMAB, J.Pharm.Pharmacol., EN, 40, 1988, 66-68
 Title:
            Effects of minaprine, a novel antidepressant, on prolactin secretion in
            the rat
 Abstract:
            The effect of minaprine, a novel psychotropic drug with antidepressant
            properties, on prolactin secretion has been investigated in the rat.On
            intraperitoneal administration (10 and 20 mg kg-1) it significantly
            decreased basal prolactin levels.In contrast, both haloperidol (1 mg
            kg-1 i.p.) and morphine (20 mg kg-1 i.p.) increased serum prolactin
            levels and daily treatment with oestradiol (100 mg kg-1 s.c.) for 4 days
            also elevated the levels.Minaprine at a dose of 20 mg kg-1 failed to
            antagonize the elevation of serum prolactin levels induced by these
            drugs.The results imply that minaprine may not exert a direct inhibitory
            action on prolactin secretion at the pituitary gland.
 CNR:
            5938853

 Author:
            Valenta, Vladimir; Protiva, Miroslav
 Reference:
            Journal, CCCCAK, Collect.Czech.Chem.Commun., EN, 52, 8, 1987,
            2095-2106
 Title:
            POTENTIAL NEUROLEPTICS OF THE ORTHOPRAMIDE SERIES;
            SYNTHESIS OF N-SUBSTITUTED
            5-(AMINOSULFONYL)-2-METHOXYBENZAMIDES
 Abstract:
            The mixed anhydride of 5-(aminosulfonyl)-2-methoxybenzoic acid (VII)
            and monoethyl carbonate reacted with benzylamine,
            1-methylpiperazine, and 1-benzylpiperazine to give the
            5-(aminosulfonyl)-2-methoxybenzamides II, IV, and V.Heating the ethyl
            ester X with 4-amino-1-methylpiperidine resulted in the amide
            III.Reaction of 5-(chlorosulfonyl)-2-methoxybenzoyl chloride (XI) with
            1-benzylpiperazine afforded
            5-(4-benzylpiperazinosulfonyl)-2-methoxybenzoic acid
            4-benzylpiperazide (VI).Compounds II-VI are analogues of the
            antidopaminergic and antiemetic agent sulpiride (I) but only the
            benzylpiperazides V and VI showed indications of psychotropic activity
            of the neuroleptic type.
 CNR:
            5561158

 Author:
            Guillaume, Jacques; Dumont, Claude; Laurent, Jacques; Nedelec,
            Lucien
 Reference:
            Journal, EJMCA5, Eur.J.Med.Chem.Chim.Ther., FR, 22, 1987, 33-44
 Title:
            (TETRAHYDRO-1,2,3,6 PYRIDINYL-4)-3 1H-INDOLES: SYNTHESE,
            PROPRIETES SEROTONINERGIQUE ET
            ANTI-DOPAMINERGIQUES
 Abstract:
            Synthesis of 3-(1,2,3,6-tetrahydro pyridin-4-yl) 1H-indoles and study of
            their serotoninergic and anti-dopaminergic properties.The synthesis of
            a series of 3-(1,2,3,6-tetrahydro pyridin-4-yl) 1H-indoles and the study
            of their serotoninergic and/or anti-dopaminergic properties are
            reported.Most of the compounds have been obtained by condensation
            of the piperidones II on the indole derivatives I in acidic or alkaline
            medium.The products have been tested in vitro for their binding to
            dopaminergic and serotoninergic receptors and in animals for gross
            behavior experiments as well as for drug interactions (apomorphine
            induced stereotypies and emesis, prochlorperazine induced catalepsy
            and 5-HT syndrome).The biological activities are largely dependent
            upon the nitrogen substitution of the tetrahydropyridinic ring and on the
            nature of the 5-substituent.The secondary amines VI exhibited, in
            general, both serotoninergic and dopaminergic agonist properties.In
            this case, the highest activity is reached for derivatives with OCH3 or
            SCH3 in the 5 position.On the other hand, the tertiary amines VII
            having an ethyl, propyl or cyclopropylmethyl on the nitrogen showed
            dopamine blocking activities.This activity becomes stronger with the
            increasing electroattractive effect of the 5-substituent (X = NO2 > Cl >
            H > SCH3 > OCH3).In the N-propyl series (VII, R = nC3H7), a direct
            correlation between the dopaminergic effect and the Hammett
            parameter sp of the substituent X has been established.The 5-methoxy
            secondary amine VI (X = 5-OCH3, RU 24969) and the 5-chloro
            N-propyl derivative VII (X = 5-Cl, R = nC3H7, RU 27592) have been
            more extensively studied in order to determine their mechanism of
            action and their possible clinical application in the field of psychotropic
            drugs.Keywords - serotoninergic agonists/ dopaminergic antagonists/
            indole derivatives/ RU 24969
 CNR:
            5670343

 Author:
            Axiotis, Stella; Sollier, Jean-Claude; Dreux, Jacques; Chermat,
            Raymond; Poncelet, Martine; Simon, Pierre
 Reference:
            Journal, EJMCA5, Eur.J.Med.Chem.Chim.Ther., FR, 22, 1987,
            293-304
 Title:
            Tetrahydropyrones-2 III. Recherce d'une activite psychostimulante
            specifique
 Abstract:
            Tetrahydropyran-2-ones III.Search for a specific psychostimulant
            activity.In a series of new tetrahydropyran-2-ones, psychostimulant
            activity without any anti-depressant effect is shown, notably in the case
            of the 3-(4-methoxy phenyl) 6-methyl 4-phenyl
            tetrahydropyran-2-one.The relative configuration and conformation of
            these compounds are determined using (1)H NMR and IR
            spectroscopies.The relationship between their psychotropic activity
            and their stereochemistry is studied.A psychostimulant activity withot
            any anti-depressant effect is found only in the case of compounds of
            the (3RS, 4RS, 6SR) configuration which are shown to adopt a
            half-chair conformation. tetrahydropyran-2-ones / configuration /
            conformation /psychostimulant activity / anti-depressant activity
 CNR:
            5675784

 Author:
            Abou-Gharbia, Magid; Patel, Usha R.; Moyer, John A.; Muth, Eric A.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 30, 6, 1987, 1100-1105
 Title:
            Psychotropic Agents: Synthesis and Antipsychotic Activity of
            Substituted b-Carbolines
 Abstract:
            A series of novel substituted b-carbolines was synthesized and tested
            for potential antipsychotic activity.Several compounds displayed
            moderate antipsychotic activity in vitro and in vivo as determined by
            relevant receptor binding assays and behavioral tests.The effect of
            substituents on antipsychotic activity was examined.The b-carbolines
            10 and 19 containing 2-(2-pyridinyl)ethyl and 2-(2-quinolinyl)ethyl side
            chains were the most potent analogues, blocking discrete trial
            conditioned avoidance responding in rats with AB50's of 23 and 10
            mg/kg, respectively.Both showed moderate activity at the D2 receptor
            sites, but they lacked oral activity.In contrast, the b-carboline 13
            containing the 4-(4-pyridinyl)butyl side chain exhibited oral activity in
            the discrete trial conditioned avoidance screen with an AB50 of 31
            mg/kg.Most compounds did not antagonize apomorphine-induced
            stereotyped behavior, which is indicative of low potential for
            extrapyramidal side effect (EPS) liability.
 CNR:
            5747160

 Author:
            Eberlein, Wolfgang G.; Trummlitz, Guenter; Engel, Wolfhard W.;
            Schmidt, Guenther; Pelzer, Helmut; Mayer, Norbert
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 30, 8, 1987, 1378-1382
 Title:
            Tricyclic Compounds as Selective Antimuscarinics. 1. Structural
            Requirements for Selectivity toward the Muscarinic Acetylcholine
            Receptor in a Series of Pirenzepine and Imipramine Analogues
 Abstract:
            The M1-selective antiulcer drug pirenzepine (1) is a tricyclic compound
            with close resemblance to tricyclic psychotropic agents such as
            imipramine (2).Despite this fact, pirenzepine is devoid of any
            psychotropic effects, exhibiting measurable antagonistic effects in
            biochemical assays and receptor binding studies only toward the
            muscarinic receptor system.To understand how different groups in
            these tricyclic molecules affect binding affinities, a set of nine
            compounds structurally related to pirenzepine (1) and imipramine (2)
            has been selected for analysis, comprising three different tricycles and
            three different side chains.The compounds were tested for their affinity
            to the imipramine and muscarinic receptors in homogenized rat cortex
            tissue.The result of these studies suggests that it is the nature and
            placement of accessory groups that determine the difference in
            receptor recognition and the binding process.In the case of pirenzepine
            (1), preferential binding toward the muscarinic receptor is brought
            about by the endocyclic amide group.From these findings a putative
            model for the explanation of selective binding of pirenzepine (1) to the
            muscarinic receptor has been derived.
 CNR:
            5747268

 Author:
            Faigle, Johann W.; Blattner, Hans; Glatt, Hansruedi; Kriemler,
            Hans-Peter; Mory, Hans; et al.
 Reference:
            Journal, HCACAV, Helv.Chim.Acta, EN, 70, 1987, 1296-1301
 Title:
            Structures and Mutagenic Properties of Products Obtained by
            C-Nitrosation of Opipramol
 Abstract:
            Reaction of the tricyclic psychotropic drug opipramol (1) with an
            excess of HNO2 affords a product mixture mutagenic for Salmonella
            typhimurium.The main product is a tetracyclic furoxan 2 (yield ca.
            80percent), resulting from nitrosation at C(10) and C(11) of
            1.Compound 2 is not mutagenic.The essential mutagen is a nitroarene
            3 formed via contraction of the central ring of 1, and nitrosation at
            C(2).Its yield is extremely low (<0.1percent).Nitroarenes have
            previously not been encountered as mutagenic products of the
            interaction of drugs with nitrite.
 CNR:
            5824598

 Author:
            Schley, J.
 Reference:
            Journal, JPPMAB, J.Pharm.Pharmacol., EN, 39, 1987, 132-134
 Title:
            Inhibitory effect of phenothiazines on the binding of <3H>perazine to
            a1-acid glycoprotein
 Abstract:
            A system is described which allows the determination of the affinity
            constant of unlabelled drugs to a1-acid glycoprotein (a1-AGP) by
            displacing <3H>perazine from the binding protein with equilibirum
            dialysis.All drugs investigated appear to bind to only one site at the
            a1-AGP molecule.From experiments, in which the chemical structure
            of the displacers was varied, the fragment 21-31 of the amino acid
            sequence appears to be a candidate for hydrophobic interactions.The
            glutamic acids 177 and 178 of the a1-AGP molecule could be involved
            in ionic interactions with the side chain of phenothiazine
            derivatives.The relevance of a11-AGP for drug binding, distribution,
            and the possible reasons for insufficient correlation between
            psychotropic plasma concentration and therapeutic response is
            discussed.
 CNR:
            5875084

 Author:
            Okpanyi, S. N.; Weischer, M. L.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., GE, 37, 1, 1987, 10-13
 Title:
            Experimental Animal Studies of the Psychotropic Activity of a
            Hypericum Extract
 Abstract:
            Extracts of Hypericum perforatum (Psychotonin M) (St.John's wort)
            with known concentrations of hypericin were tested in several models
            generally accepted as screening methods in experimental animal
            studies for the recognition of psychotropic, and in particular of
            antidepressant activity.Hypericum extract enhanced the exploratory
            activity of mice in a foreign environment, significantly prolonged the
            narcotic sleeping time dose-dependently, and within a narrow dose
            range exhibited reserpine antagonism.Similar to most other
            antidepressants, hypericum extract enhanced significantly the activity
            of mice in the water wheel test and after a prolonged daily
            administration decreased aggressiveness in socially isolated male
            mice.The presented data in addition to the already proven clinical
            efficacy justify the use of standardised Hypericum extract in the
            treatment of mild to moderate depression.Key words: Antidepressant;
            Hypericin; Hypericum perforatum; Phytotherapeutics; Psychotonin M
 CNR:
            5877962

 Author:
            Gruenberger, J.; Linzmayer, L.; Cepko, H.; Saletu, B.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., GE, 37, 3, 1987, 357-360
 Title:
            Lichtevozierte dynamische Pupillometrie zur Differenzierung
            psychotroper Substanzen
 Abstract:
            On the Differentiation of Psychotropic Drugs by Means of Light-Evoked
            Dynamic Pupillometry. In a double-blind placebo-controlled study 100
            mg zotepine (neuroleptic) were administered to 15 young healthy
            volunteers; another 15 volunteers received 200 mg moclobemide (Ro
            11-1163) (MAO-inhibitor).At the certain days of investigation the
            light-evoked pupillary reactions were recorded prior to and 2, 4, 6, and
            8 h after medication.Using the dynamic pupillometric method it was
            possible to differentiate between zotepine and moclobemide in view of
            autonomus activation. Key words: Moclobemide, clinical
            studies.Psychotropics.Pupillometry, light-evoked dynamic.Ro
            11-1163.Zotepine, clinical studies
 CNR:
            5880407

 Author:
            Porsolt, R.D.; Lenegre, A.; Avril, I.; Lancrenon, S.; Steru, L.; Doumont,
            G.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 37, 4, 1987, 388-394
 Title:
            Psychopharmacological Profile of the New Cognition Enhancing Agent
            Exifone in the Mouse
 Abstract:
            Hexahydro-2,3,4,3',4',5'-benzophenone (exifone, Adlone), a novel
            compound proposed for treating cognitive dysfunction in geriartic
            patients, was tested in a battery of standard psychopharmacological
            tests in the mouse.The results indicate that the compound was
            non-toxic and induced no signs of overt stimulation or sedation after
            acute administration of oral doses up to 1024 mg/kg.The compound
            was devoid of anxiolytic, anticonvulsant or classical neuroleptic activity
            and did not antagonize the effects of reserpine or a high dose of
            apomorphine, two tests indicative of classical antidepressant
            activity.On the other hand, exifone clearly decreased the duration of
            immobility in the tail suspension test and antagonized the hypothermia
            induced by a low dose of apomorphine.The compound shortened the
            duration of barbital induced sleep without affecting the duration of
            sleep induced by pentobarbital.The effects observed suggest that
            exifone is not devoid of psychotropic activity and might possess some
            properties of an atypical antidepressant. - Keywords:
            Adlone.Atropine.Cognition enhancing
            agents.Desipramine.Diazepam.Exifone,
            psychopharmacology.Pimozide
 CNR:
            5880845

 Author:
            Ulrich, G.; Kriebitzsch, R.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., GE, 37, 4, 1987, 472-481
 Title:
            Ein rechnerstuetztes visuomotorisches Tracking-Verfahren zur
            trennscharfen Objektivierung zentralnervoeser Pharmakoneffekte
 Abstract:
            A Computer-assisted Visuomotor Tracking Device for Selective
            Objectivation of Central-nervous Drug Effects In order to overcome the
            well-known shortcomings of current psychometry especially for the
            objectivation of the effects of psychotropic drugs, a computer-assisted
            visuomotor tracking device has been developed.The subjects' task is
            to closely pursue a target signal which moves continuously but at
            variable speed on a TV-screen by directing a response signal on the
            screen with a small joystick.In contrast to conventionally used
            visuomotor tracking tasks the mean efficiency of the performance is
            measured exactly in bit/s from the difference between target and
            response signal.First applications showed: 1.The selectivity of the
            procedure depends decisively on the degree of difficulty of the target
            signal, i.e., the veocity of the target signal. 2.There is no substantial
            learning effect with re-tests at a 1-week interval. 3.When testing over
            longer periods (400 s) a decrement of performance must be taken into
            consideration. - Keywords: Central-nervous drug effects,
            objectivation.Drugs, objectivation of subtle central-nervous effects.
            visuomotor tracking device, computer-assisted
 CNR:
            5880865

 Author:
            Andrasi, F.; Horvath, K.; Sineger, E.; Berzsenyi, P.; Borsy, J.; et al.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 37, 10, 1987, 1119-1124
 Title:
            Neuropharmacology of a New Psychotropic 2,3-Benzodiazepine
 Abstract:
            1-(3-Chlorophenyl)-4-methyl-7,8-dimethoxy-5H-2,3-benzodiazepine
            (GYKI 51189) is a new analogue of tofisopam.Due to the novel
            chemical structure this molecule displays a peculiar spectrum of
            pharmacological activity.In many respects tofisopam and its new
            analogue differ from the traditional 1,4-benzodiazepines, e.g. in that
            they possess selective anxiolytic action without muscle relaxant and
            anticonvulsive activity, as well as they do not show any affinity for the
            1,4-benzodiazepine receptors.This new compound exerts more
            pronounced anxiolytic potency than tofisopam.In addition to its main
            action it possesses significant antidepressant activity.It attenuates
            psychomotor agitation and exerts significant antiaggressive effect by
            reducing both spontaneous and induced aggressiveness.Vegetative
            responses (rise in blood pressure and heart rate) induced by electric
            stimulation of the hypothalamus are also inhibited by this compound,
            while motor functions remain unaffected and no somnolence is
            induced.The new tofisopam analogue fails to exert any potentiating
            effect either on ethanol or on barbiturates.GYKI-51189 has a highly
            favourable therapeutic index and only few side effects.Neither
            tolerance nor dependence was observed during the chronic
            toxicological investigations.Key words: 2,3-Benzodiazepines;
            Chlordiazepoxide;
            1-(3-Chlorophenyl)-4-methyl-7,8-dimethoxy-5H-2,3-benzodiazepine,
            neuropharmacology; GYKI 51189; Tofisopam, analogue,
            neuropharmacology
 CNR:
            5883877

 Author:
            Lipkowitz, Kenny; Burkett, Anthony; Landwer, Jo
 Reference:
            Journal, HTCYAM, Heterocycles, EN, 24, 10, 1986, 2757-2770
 Title:
            THEORETICAL STUDIES OF PSYCHOTROPIC DRUGS.
            QUESTIONING THE IMPORTANCE OF FLEX-ANGLE IN DRUG
            EFFICACY
 Abstract:
            MNDO calculations indicate that hetero-substituted
            9,10-dihydroanthracenes are inherently planar molecules.Ring
            puckering is a very low energy process that can arise from
            intramolecular effects, e.g. peri-and/or transannular interactions as well
            as from intermolecular interactions like crystal packing forces.It is
            concluded that the angle of flexure, determined crystallographically
            and used as a descriptor of drug activity in several important CNS
            drugs, should be used with caution or not be used at all.
 CNR:
            5698710

 Author:
            Omarov, T. T.; Zaks, A. S.; Kapitonenko, T. A.; Baisalbaeva, S. A.;
            Sultanbaeva, B. M.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 20, 12, 1986,
            838-840
 Title:
            SYNTHESIS OF COMPLEX AZABICYCLO<3.3.1>NONANE ESTERS
            AND THEIR PSYCHOTROPIC ACTIVITY
 Abstract:
 CNR:
            5702533

 Author:
            Akhundov, R. A.; Zhmurenko, L. A.; Glozman, O. M.; Voronina, T. A.;
            Zagorevskii, V. A.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 20, 1, 1986,
            32-35
 Title:
            SYNTHESIS AND PSYCHOTROPIC ACTIVITY OF AMIDES OF
            2-AMINONICOTINIC ACID
 Abstract:
 CNR:
            5702704

 Author:
            Kostyanovskii, R. G.; Shustov, G. V.; Nabiev, O. G.; Denisenko, S. N.;
            Sukhanova, S. A.; Lavretskaya, E. F.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 20, 6, 1986,
            385-388
 Title:
            SYNTHESIS AND PSYCHOTROPIC ACTIVITY OF FUNCTIONALLY
            SUBSTITUTED DIAZIRIDINES AND BISDIAZIRIDINES
 Abstract:
 CNR:
            5703236

 Author:
            Salima, T. A.; Yu, V. K.; Korablev, M. V.; Praliev, K. D.; Kurbat, N. M.;
            Sokolov, D. V.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 20, 6, 1986,
            397-400
 Title:
            SYNTHESIS, ANALGESIC, AND PSYCHOTROPIC PROPERTIES OF
            SOME 1-<2-ETHOXYETHYL>-3-METHYLPIPERIDIN-4-ONES. XX.
 Abstract:
 CNR:
            5703239

 Author:
            Praliev, K. D..; Salima, T. A.; Zhilkibaev, O. T.; Korablev, M. V.;
            Sadykov, A. O.; et al.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 20, 9, 1986,
            611-614
 Title:
            SYNTHESIS OF PIPERIDINE AND DECAHYDROQUINOLINE
            DERIVATIVES, THEIR ANALGESTIC AND PSYCHOTROPIC
            PROPERTIES. XXI. 1-METHYL-4-VINYLETHYNYLPIPERIDIN-4-OL
            AND ITS ESTERS
 Abstract:
 CNR:
            5703470

 Author:
            Czerniawski, Marian; Bialowas, Barbara; Kowalska, Elzbieta
 Reference:
            Journal, PJCHDQ, Pol.J.Chem., EN, 60, 1-3, 1986, 185-191
 Title:
            COLLOIDAL PROPERTIES OF PHENOTHIAZINE COMPOUNDS.
            PART II. THE INFLUENCE OF THIORIDAZINE HYDROCHLORIDE
            CONCENTRATION ON THE VALUE OF DZETA-POTENTIAL OF
            AgBr SOL
 Abstract:
            By means of microelectrophoretic method the influence of
            concentration of an aqueous thioridazine hydrochloride solution on the
            changes in value of colloidal AgBr dzeta-potential has been
            studied.The method has been found useful for studying the selective
            adsorption of the psychotropic compound-thioridazine
            hydrochloride.The results obtained enable us to conclude about the
            way the drug studied acts upon the nerve tissue.
 CNR:
            5775343

 Author:
            Boeke-Kuhn, K.; Knappen, F.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 36, 3a, 1986, 606-609
 Title:
            Interactions of Brotizolam and Diazepam with Some Psychotropic Drugs on Motor
            Perfomance in Mice
 Abstract:
            The interaction of brotizolam
            (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno<3,2-f>-1,2,4-triazolo<4,3-a>-1,4-diazepine,
            We 941, Lendormin), and diazepam with ethanol, phenobarbital, haloperidol and
            desipramine was investigated in a motor performance test (rotarod) in mice.Brotizolam and
            diazepam were tested at dose levels which partially impaired the motor performance.In
            combination with ethanol and phenobarbital only the anticipated additive effects was
            observed.Brotizolam and diazepam partially overcame the cataleptic effect of haloperidol.A
            combined treatment with brotizolam and desipramine did not alter the effect obtained with
            brotizolam alone.In a second experiment the loss of righting reflexes induced by ethanol and
            hexobarbital was prolonged by brotizolam and diazepam depending on the dose.From this it
            is concluded that in combination with ethanol brotizolam and diazepam may be effective at
            antiemotional and anticonvulsant doses.In combination with hexobarbital brotizolam is
            expected to have a greater "therapeutic range". - Key words: Brotizolam, interaction with
            psychotropics; Diazepam, interaction with psychotropics; Diazepines; Hypnotics;
            Lendormin; Psychotropics; We 941
 CNR:
            5795756

 Author:
            Gruenberger, J.; Linzmayer, L.; Cepko, H.; Saletu, B.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., GE, 36, 1, 1986, 141-146
 Title:
            Pupillometry in Studies of Psychotropic Substances
 Abstract:
            Considering data of various clinical pharmacological studies, in which
            computer-assisted pupillometry was utilized, we investigated the
            following questions: 1.What are the effects of drugs of 7
            psychopharmacological classes on the human pupil? 2.Do
            dose-efficacy and time-efficacy curves based on pupillary variables
            provide cues about pharmacodynamic properties of psychotropic
            substances? 3.Is there a relationship between pupillometric and critical
            flicker frequency measures? 4.Is there a relation between pupillometric
            and quantitative electroencephalographic changes? 5.Are there
            correlations between static pupillometric and pharmacokinetic (e.g.
            blood levels) variables? Our investigations demonstrated that static
            pupillometry - utilized in the described manner and under certain
            experimental conditions - provide valuable information about effects of
            psychotropic drugs on the central and autonomous nervous system. -
            Key words: Hysteresis * Psychotropic drugs, clinical
            pharmacodynamics, clinical pharmacokinetics * Static pupillometry
 CNR:
            5868237

 Author:
            Hoeglund, Peter; Eriksson, Margareta; Christensson, Erik G.
 Reference:
            Journal, JPPMAB, J.Pharm.Pharmacol., EN, 38, 4, 1986, 861-863
 Title:
            Antiarrhythmic effect of amperozide, a novel psychotropic compound
            with class III antiarrhythmic properties, on digoxin-inducedarrhythmias
            in the guinea-pig
 Abstract:
            Amperozide is a novel psychotropic compound with specific effect in
            limbic brain areas.Preliminary findings have also indicated an
            antiarrhythmic effect in-vitro.Injections of saline, amperozide,
            melperone, thioridazine, bretylium or lignocaine, were given i.p. to
            anaesthetized guinea-pigs, which 10 min later were given digoxin s.c.
            to induce arrhythmia.In a series of control experiments none of these
            compounds caused arrhythmia in combination with the vehicle of
            digoxin.The time to arrhythmia was significantly prolonged after
            treatment with amperozide, melperone and bretylium compared with
            saline, but there were no differences betweenthe treatments.The
            digoxin concentrations in plasma at death varied considerably within
            the groups and no statistical significance was found.
 CNR:
            5877192

 Author:
            Nielsen, Flemming E.; Pedersen, Erik B.
 Reference:
            Journal, JHTCAD, J.Heterocycl.Chem., EN, 22, 1985, 1693-1701
 Title:
            Annulated 1,2,3-Triazoles. Synthesis of
            1,2,3-Triazolo<4,5-b><1,5>benzoxazepin-10(9H)-ones and
            10-(4-Substituted-1-piperazinyl)-1,2,3-triazolo<4,5-b><1,5>benzoxazepines
 Abstract:
            10-(4-Substituted-1-piperazinyl)-1,2,3-triazolo<4,5-b><1,5>benzoxazepines
            11 were prepared in a three-step synthesis starting from easily available
            5-chloro-1,2,3-triazole-4-carbonyl chlorides 7 by titanium tetrachloride
            catalyzed condensation of N-(substituted)piperazines with
            1,2,3-triazolo<4,5-b><1,5>benzoxazepin-10(9H)-ones 10 formed by ring
            closure of the intermediate amides 9.Although lactams 10 were obtained as
            the sole product of the cyclisation at 80 deg C, the unexpected by-products
            13 and 14 were formed in addition to 10c at 150 deg C from 9c.The
            4-methoxybenzyl group in 11j was easily removed by solvolyses in
            TFA.Compounds 1 1 d-f and 11i were tested for psychotropic activity.
 CNR:
            5563696

 Author:
            Astoin, Jacques; Lepage, Francis; Poisson, Micheline
 Reference:
            Journal, EJMCA5, Eur.J.Med.Chem.Chim.Ther., FR, 20, 5, 1985,
            495-500
 Title:
            Synthese et proprietes antidepressives de nouveaux amino-alcenols
 Abstract:
            The preparation and pharmacological screening of
            styrylethanolamines enabled us to determine more precisely the
            psychotropic activity of the alcenol structure.Results show that this
            series exerts a thymoanaleptic action, and more particularly the
            compounds substituted in the para position on their phenyl group and
            bearing a morpholine group.An antidepressant action can also be
            expected from some of them which have revealed themselves as
            antireserpinics, anticataleptics and potentializers of the yohimbine
            toxicity.Four compounds are of special interest in this connection.Two
            of them, i.e., (4-methoxy phenyl)-1 4-morpholino 1-butene 3-ol 14 and
            (4-chloro phenyl)-1 4-morpholino 1-butene 3-ol 28 have been selected
            for further study.
 CNR:
            5604193

 Author:
            Chretien, Jacques R.; Szymoniak, Jan; Dubois, Jacques-Emile;
            Poirier, Marie-France; Garreau, Martine; Deniker, Pierre
 Reference:
            Journal, EJMCA5, Eur.J.Med.Chem.Chim.Ther., FR, 20, 4, 1985,
            315-325
 Title:
            Etudes S.A.R. et banques de donnees pharmacologiques: une
            methode DARC de CAO appliquee aux neuroleptiques
 Abstract:
            In seeking to identify the structural parameters involved in the
            neuroleptic activity of 116 compounds, a search of the PSYCHO-DATA
            bank containing information related to the structure of 1 681
            psychotropic agents, was conducted by means of a CAD method
            adapted to deal with heterogeneous populations of compounds.This
            method is based on the FREL (FRagment with an Environment which
            is Limited) concept from the DARC System.By conducting a statistical
            study of the distribution of these structural fragments in the neuroleptic
            compounds, in the structurally analogous non-neuroleptic compounds,
            and in all other bank compounds, three categories of activity can be
            descerned for the FRELs of these neuroleptic compounds: neuroleptic
            neurophobic and neutral.The extent to which the method can be
            generalized and the possibility of detecting finer structural properties
            related to neuroleptic activity are illustrated on a homogeneous
            population of compounds, neuroleptic and non-neuroleptic
            phenothiazines.Key-words: Neuroleptic activity - Neuroleptic
            compounds - Structure Activity Relationships (SAR) - Data bank -
            C.A.O. - System expert.
 CNR:
            5672301

 Author:
            Tichniouin, Mohamed; Sauleau, Jean; Sauleau, Armelle; Lacroix,
            Pierre
 Reference:
            Journal, EJMCA5, Eur.J.Med.Chem.Chim.Ther., FR, 20, 2, 1985,
            181-186
 Title:
            Synthese, activite psychotrope, effets sur les arythmies experimentales
            d'hydroxyhydrazines insaturees
 Abstract:
            The synthesis of a series of a-ethylenic hydrazinoalcohols via the ring
            cleavage of a-ethylenic epoxides by hydrazines was described.The
            competitive attack by the nucleophiles at the less substituted carbon
            atom (compounds Y), or at the carbon atom-2 (compounds Z) are
            discuted.The psychotropic and antidysrhythmic activities of these
            compounds was evaluated.
 CNR:
            5675001

 Author:
            Korablev, M. V.; Praliev, K. D.; Salita, T. A.; Zhilkibaev, O. T.; Kurbat N.
            M.; et al.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 19, 4, 1985,
            252-256
 Title:
            SYNTHESIS OF PIPERIDINE AND DECAHYDROQUINOLINE
            DERIVATIVES: THEIR ANALGETIC AND PSYCHOTROPIC
            PROPERTIES. XVIII. 1-METHYL-4-ACETYLPIPERIDIN-4-OL AND
            ITS ESTERS
 Abstract:
 CNR:
            5701860

 Author:
            Praliev, K. D.; Esenalieva, M. Z.; Krasnomolova, L. P.; Kurilenko, V. M.;
            Mekhova, G. M.; Sokolov, D. V.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 19, 2, 1985, 117-121
 Title:
            SYNTHESIS OF PIPERIDINES AND DECAHYDROQUINOLINES, AND
            THEIR ANALGETIC AND PSYCHOTROPIC PROPERTIES. XVII.
            STEREOISOMERS OF
            1-<3-PHENYLPROPYN-2-YL>-2,3-DIMETHYL-4-ETHYNYLPIPERIDIN-4-OL
            AND THEIR ACETATES
 Abstract:
 CNR:
            5702905

 Author:
            Papsuevich, O. S.; Chipens, G. I.; Bakharev, V. D.; Petrova, T. A.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 19, 1, 1985,
            24-28
 Title:
            SYNTHESIS AND PSYCHOTROPIC PROPERTIES OF THE
            TETRAPEPTIDE OF HUMAN INTERFERON-a2-(122-125)
 Abstract:
 CNR:
            5703421

 Author:
            Nagarajan, K.; David, J.; Bhat, G. A.
 Reference:
            Journal, IJSBDB, Indian J.Chem.Sect.B, EN, 24, 1985, 840-844
 Title:
            Synthesis of 10,11-Dihydrodibenz<b,f><1,4>oxazepine Derivatives as
            Potential Anticonvulsant and Psychotropic Agents
 Abstract:
            Several acyl, carbamoyl and thiocarbamoyl derivatives of
            10,11-dihydrodibenz<b,f><1,4>oxazepine, most of them carrying either
            a nitro or amino group at position-2 have been synthesized as
            analogues of carbamazepine (38) and evaluated as anticonvulsants
            associated with potential neuroleptic activity.Among these,
            10,11-dihydro-2-nitrodibenz<b,f><1,4>oxazepine-10-carboxylic acid
            hydrazide (11) and
            2-amino-10-dimethylcarbamoyl-dibenz<b,f><1,4>oxazepine (24) have
            moderate activity in the electroshock test but are inactive against
            chemoshock.
            10,11-Dihydro-10-thiocarbamoyldibenz<b,f><1,4>oxazepine (2) is
            active against electroshock as well as against strychnine-induced
            seizures, has some analgesic activity and also exhibits neuroleptic
            properties, but the overall profile of 2 does not present any advantages
            over the well known drug, carbamazepine (38).
 CNR:
            5703721

 Author:
            Petkov, V. V.; Grahovska, T.; Petkov, V. D.; Konstantinova, E.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 35, 12, 1985, 1778-1781
 Title:
            Effects of Meclofenoxate on the Level and Turnover of Biogenic
            Monoamines in the Rat Brain
 Abstract:
            The level and turnover of biogenic monoamines in some rat brain
            structures were determined after treatment with meclofenoxate at a
            dose of 50 mg/kg administered i.p. two times a day (9 a.m. and 5 p.m.)
            for 5 days.Meclofenoxate decreased dopamine (DA) turnover in the
            frontal cortex and striatum and highly increased its in the
            hypothalamus.The DA level significantly declined in the striatum,
            tended to decline in the cortex and significantly rose in the
            hypothalamus.The noradrenaline (NA) turnover and level in the cortex
            and striatum were decreased.Meclofenoxate decreased serotonin
            (5-HT) turnover in the cortex, striatum and hypothalamus and
            increased it in the pons.At the same time, the 5-HT level rose in the
            cortex, striatum and pons and declined in the hypothalamus.These
            results suggest the neurochemical basis of the psychotropic and
            neuroendocrine effects of meclofenoxate.- Key words: Dopamine;
            Meclofenoxate; Noradrenaline; Psychotropic drugs; Serotonin
 CNR:
            5793872

 Author:
            Stefancich, G.; Artico, M.; Corelli, F.; Massa, S.; Pantaleoni, G. C.; et al.
 Reference:
            Journal, FRPSAX, Farmaco Ed.Sci., IT, 40, 12, 1985, 930-941
 Title:
            RICERCHE SU NUOVI AGENTI PSICOTROPI. Nota II - Sintesi ed attivita
            farmacologica di derivati della 5H-pirrolo<1,2-b><1,2,5>benzotriazepina.
 Abstract:
            Bischler-Napieralski intramolecular cyclization of
            N-(2-aroylaminophenyl)-N-methyl-1H-pyrrol-1-amines and reaction of
            arylaldehydes on N-(2-aminophenyl)-N-methyl-1H-pyrrol-1-amine
            furnished 11-aryl-5-methyl-5H-pyrrolo<1,2-b><1,2,5>benzotriazepines and
            11-aryl-10,11-dihydro-5-methyl-5H-pyrrolo<1,2-b><1,2,5>benzotriazepines
            respectively.The latter reaction required in some cases the use of
            p-toluenesulphonic acid as a catalyst. - The new tricyclic derivatives
            described were tested for pharmacological evaluation of their psychotropic
            activity.
 CNR:
            5911742

 Author:
            Valdes, Leander J.; Butler, William M.; Hatfield, George M.; Paul, Ara
            G.; Koreeda, Masato
 Reference:
            Journal, JOCEAH, J.Org.Chem., EN, 49, 1984, 4716-4720
 Title:
            Divinorium A, a Psychotropic Terpenoid, and Divinorin B from the
            Hallucinogenic Mexican Mint Salvia Divinorum
 Abstract:
 CNR:
            5575991

 Author:
            Moriyasu, Masataka; Endo, Masaru; Hashimoto, Yohei; Koeda, Takemi
 Reference:
            Journal, CPBTAL, Chem.Pharm.Bull., EN, 32, 2, 1984, 600-608
 Title:
            High-Performance Liquid Chromatographic Determination of Organic
            Substances by Metal Chelate Derivatization. II. Microdetermination of
            Methamphetamine and Amphetamine
 Abstract:
            The reaction of Ni(II) dithiocarbamate chelate formation was applied as
            a color reaction in high-performance liquid chromatography (HPLC)
            analysis of aliphatic primary and secondary amines.The reaction
            proceeded quantitatively and almost instantaneously at room
            temperature in alkaline media.The deep yellow (log e = 4.5 at 325 nm)
            reaction products were extractable with organic solvents and gave
            sharp peaks on both normal-phase and reverse-phase
            chromatography.This method was applied to the microdetermination of
            stimulant drugs, e.g. methamphetamine and amphetamine, in urine,
            and as little as 1 ng of these drugs could be detected.Keywords -
            methamphetamine; amphetamine; aliphatic primary amine; aliphatic
            secondary amine; Ni(II) dithiocarbamate; psychotropic drug;
            high-performance liquid chromatography.
 CNR:
            5682834

 Author:
            Praliev, K. D.; Belikova, N. A.; Kurilenko, V. M.; Khlienko, Zh. N.;
            Moiseeva, L. M.; Sokolov, D. V.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 18, 10, 1984,
            697-702
 Title:
            SYNTHESIS OF DERIVATIVES OF PIPERIDINE AND
            DECAHYDROQUINOLINE, AND THEIR ANALGESIC AND
            PSYCHOTROPIC PROPERTIES. XVI. NEW N-ANALOGS OF
            DESMETHYLPRODINE
 Abstract:
 CNR:
            5701843

 Author:
            Voronina, T. A.; Glozman, O. M.; Orlova, E. K.; Troitskaya, V. S.;
            Nerobkova, L. N.; et al.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 18, 11, 1984,
            750-754
 Title:
            SYNTHESIS AND PSYCHOTROPIC ACTIVITY OF
            2-PHENOXYPROPIONAMIDOXIMES AND THEIR ANALOGS
 Abstract:
 CNR:
            5702011

 Author:
            Grinev, A. N.; Shvedov, V. I.; Krichevskii, E. S.; Romanova, O. B.;
            Altukhova, L. B.; et al.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 18, 2, 1984,
            94-98
 Title:
            SYNTHESIS AND PSYCHOTROPIC ACTIVITY OF PYRAZIDOLE
            ANALOGS
 Abstract:
 CNR:
            5702434

 Author:
            Ahuja, Y. R.; Jaju, M.; Saxena, R.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 34, 6, 1984, 699-701
 Title:
            Cytogenetic Effects of Psychotropic Drug Haloperidol on Human
            Lymphocytes
 Abstract:
            Haloperidol is used for long-term therapy of psychiatric disorders.The
            cytogenetic effect of this drug was studied on human chromosomes in
            lymphocyte cultures in vitro and in vivo.There was no increase in the
            chromosomal aberration frequency in vitro with haloperidol at
            concentrations equivalent to plasma level and slightly higher than
            plasma level.However, a significant increase in the frequency of
            chromosome aberrations was seen in patients on therapeutic doses of
            haloperidol as compared to the two types of controls: 1.Psychiatric
            patients before starting the drug therapy and 2. normal healthy
            individuals from the general population.The most frequently observed
            aberrations were chromatid gaps and breaks.Our study indicates that
            haloperidol is not clastogenic in vitro at plasma concentration but
            significantly clastogenic in vivo. - Key words: Haloperidol, clinical
            pharmacology; Lymphocytes, cytogenetic effects on human;
            Psychotropics
 CNR:
            5794505

 Author:
            Hoffmeister, F.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., GE, 34, 9a, 1984, 1096-1107
 Title:
            Dependence Liability of Analgesic and Psychotropic Drugs
 Abstract:
            The dependence liability of analgesic and psychotropic drugs as
            assessed in animal experiments is described.It is demonstrated that
            the abuse liability of a given drug does not only depend on its
            pharmacological or psychopharmacological profile of actions.The
            abuse liability of a drug is, however, greatly influenced by
            environmental variables, motivation to self-administration of a drug as
            well as previous drug exposure.Correlations between dependent
            behavior of animals and dependent behavior of men are discussed. -
            Key words: Analgesics, dependence liability; Assessment in animal
            experiments; Psychotropics, dependence liability
 CNR:
            5796468

 Author:
            Hawes, E. M.; Shetty, H. U.; Cooper, J. K.; Rauw, G.; McKay, G.; Midha, K. K.
 Reference:
            Journal, JPMSAE, J.Pharm.Sci., EN, 73, 2, 1984, 247-250
 Title:
            Radioimmunoassay for Psychotropic Drugs III: Synthesis and Properties of Haptens
            for Trifluoperazine and Fluphenazine
 Abstract:
            For the development of radioimmunoassay procedures for trifluoperazine and
            fluphenazine, three haptens, N-(2-carboxyethyl)desmethyltrifluoperazine,
            N-(4-carboxybutyl)desmethyltrifluoperazine, and
            10-<3-(4-carboxyethylpiperazinyl)-3-oxopropyl>-2-trifluoromethyl-10H-phenothiazine,
            were synthesized and characterized.Each hapten was coupled to bovine serum
            albumin, and the number of hapten residues per mole of bovine serum albumin was
            calculated by UV spectrophotometric methods.Antibodies to each hapten-protein
            conjugate were developed in rabbits, and titers of the antisera were checked by
            evaluating their binding characteristics to the tritiated drug.
 CNR:
            5835814

 Author:
            Bressolle, Francoise; Bres, Janine; Blanchin, Marie Dominique;
            Gomeni, Roberto
 Reference:
            Journal, JPMSAE, J.Pharm.Sci., EN, 73, 8, 1984, 1128-1136
 Title:
            Sulpiride Pharmacokinetics in Humans After Intramuscular
            Administration at Three Dose Levels
 Abstract:
            Pharmacokinetics of the disinhibitory psychotropic agent sulpiride was
            investigated in 9 healthy male subjects after intramuscular
            administrations of 50, 100, and 200 mg in a 3 x 3 Latin square
            design.Plasma and urine concentrations were measured by HPLC for
            36 and 48 h, respectively.The lowest detectable concentration was 10
            ng/mL.Plasma concentration versus time and urinary excretion rate
            versus time curves were consistent with an open two-compartment
            body model, where mean +/-SD apparent half-lives of the adsorption
            from muscule, l1 distribution, and l2 elimination phases were 6.96 +/-
            2.64 min, 0.220 +/- 0.120 h, and 6.74 +/- 2.67 h, respectively.The initial
            volume of distribution was 0.145 +/- 0.063 L/kg, the steady-state
            volume of distribution was 0.639 +/- 0.184 L/kg, and the total clearance
            was 89.8 +/- 22.3 mL/min.The microscopic rate constants were k12 =
            2.53 +/- 1.13 h-1, k21 = 0.674 +/- 0.197 h-1, and k10 = 0.635 +/- 0.298
            h-1.Comparison of total clearance (89.8 mL/min), renal clearance (83.0
            mL/min), and renal clearance of unbound drug (97.6 mL/min, f = 0.15)
            indicated that sulpiride is mainly excreted unchanged by the renal
            route, 93.1 +/- 6.6percent of the administered dose being recovered
            unchanged in urine.Statistical evaluation of all the above parameters,
            determined at the three dosage levels, did not show anyl variations
            related to dose; the pharmacikinetics of sulpiride, over the dose range
            tested, was therefore linear and independent of dose.The
            two-compartment body model proposed was validated by digital
            computer simulation on a small digital computer (32K).
 CNR:
            5869155

 Author:
            Ferretti, P.; Algeri, S.; Benfenati, F.; Cimino, M.; Ferretti, C.; et al.
 Reference:
            Journal, JPPMAB, J.Pharm.Pharmacol., EN, 36, 1984, 48-50
 Title:
            Biochemical effects of minaprine on striatal dopaminergic neurons in
            rats
 Abstract:
            The biochemical effects of minaprine, a new psychotropic drug, were
            investigated on striatal dopaminergic neurons in the rat.Minaprine did
            not displace <3H>spiperone in-vitro binding from striatal membranes
            but had clear effects on dopamine (DA) metabolites.Homovanillic acid
            (HVA) and dihydroxyphenylacetic acid (DOPAC) were significantly
            decreased in a dose-dependent manner after intraperitoneal
            administration of minaprine 30 min before killing.In rats injected with
            minaprine 15 mg kg-1 i.p. at different intervals, the decrease in striatal
            HVA and DOPAC was time-dependent and a concomitant rise in
            3-methoxytryramine (3-MT) concentrations was observed.The
            maximum of these effects was reached 30 min after minaprine.When
            administered 5 min after a monoamineoxidase (MAO) inhibitor
            (pargyline, 100 mg kg-1 i.p.) and 30 min before killing, minaprine did
            not affect pargyline-induced changes in HVA, DOPAC and 3-MT
            levels.This together with other data suggests that minaprine affects DA
            metabolism by acting, at least partially, at presynaptic level through
            in-vivo inhibition of MAO activity.
 CNR:
            5941307

 Author:
            Agarwal, Rajesh; Chaudhary, Chapla; Misra, V. S.
 Reference:
            Journal, IJSBDB, Indian J.Chem.Sect.B, EN, 22, 3, 1983, 308-310
 Title:
            Synthesis of
            2-Aryl-1-(4-morpholinophenyl)-4-(3,4-disubstituted-benzylidene)imidazolin-5-ones
            as CNS Active Agents
 Abstract:
            The title compounds (IVa-l) have been prepared by the action of
            p-morpholinoaniline (II) on appropriate oxazolin-5-ones (III) in the presence of
            anhyd.ZnCl2 or super dry pyridine.However, the interaction of II and III in ordinary
            pyridine/benzene or in the absence of anhydr.ZnCl2 gives
            p-morpholinophenylcarboxamides (V) of a-arylcarboxamido-b-(3,4-disubstituted
            phenyl)acrylic acids indicating the reaction of II and III to be moisture
            sensitive.Compounds IV have been found to be nontoxic and psychotropic.
 CNR:
            5576505

 Author:
            Barbe, Jacques; Andrews, Peter R.; Lloyd, Edward J.; Brouant, Pierre;
            Soyfer, Jean-Claude; et al.
 Reference:
            Journal, EJMCA5, Eur.J.Med.Chem.Chim.Ther., FR, 18, 6, 1983,
            531-534
 Title:
            Individualisation des supports structuraux des actions sedative et
            anti-H1
 Abstract:
            The conformations of some quinuclidinyl substituted compounds were
            studied by molecular energy calculations.Results are in agreement
            with a structural pattern, previously suggested in order to explain the
            polybiovalency of psychotropic agents.It is therefore proposed that the
            sedative activity of drugs requires a stereochemical interaction with
            central H3 histamine receptors, structurally different from the peripheral
            H1 receptors.Basic geometrical requirements for activity are given in
            both cases.Key-words: Histamine (peripheric Receptors). -
            Phenothiazines (Conformations). - Sedative Activity (structural
            Support). - Polybiovalence (Models).
 CNR:
            5611096

 Author:
            Poplavskaya, I. A.; Kurmangalieva, R. G.; Khalilova, S. F.; Zaks, A. S.;
            Kapitonenko, T. A.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 17, 3, 1983,
            182-186
 Title:
            SYNTHESIS AND PSYCHOTROPIC ACTIVITY OF
            N-ARYLACETYLFORMAMIDOXIME HYDRAZONES
 Abstract:
 CNR:
            5642877

 Author:
            Fischer, W.; Boehme, H.-R.
 Reference:
            Journal, PHARAT, Pharmazie, EN, 38, 11, 1983, 749-751
 Title:
            Investigations on Unspecific, Intestinal Elimination in the Case of
            Poisoning with Psychotropic Drugs
 Abstract:
            Anticholinergic and antiserotonergic activities of the psychotropic drugs
            chlorpromazine, fluphenazine, imipramine and promethazine have
            been investigated quantitatively on the guinea-pig isolated
            ileum.Additional experiments were made to assure the comparability
            of receptor activity with human intestinal (ileum) preparations.Each of
            the four compounds exhibited a marked blocking potency both on
            muscarinic and serotonergic receptors.The antagonism was found to
            be slowly reversible and non-cpmpetitive in higher drug
            concentrations.Sodium sulfate often recommended incases of
            poisoning with these drugs was nearly ineffective for evoking
            contractions in model investigations with drug concentrations which
            can be found in practical clinical conditions.
 CNR:
            5689687

 Author:
            Praliev, K. D.; Sydykov, B. T.; Sokolov, D. V.; Kurilenko, V. M.; Khlienko, Zh. N.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 17, 9, 1983, 622-624
 Title:
            SYNTHESIS OF PIPERIDINES AND DECAHYDROQUINOLINES, AND THEIR
            ANALGESIC AND PSYCHOTROPIC PROPERTIES. XI.
            1-<3'-PHENYL-2'-PROPYNYL>-2,4-DIPHENYL-3-METHYL-4-HYDROXYPIPERIDINE
            AND ITS DERIVATIVES
 Abstract:
 CNR:
            5702409

 Author:
            Andronati, S. A.; Voronina, T. A.; Chepelev, V. M.; Korotenko, T. I.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 17, 11, 1983,
            769-772
 Title:
            INFLUENCE OF
            5-METHYLl-1,2-DIHYDRO-3H-BENZDIAZEPIN-2-ONES ON THE
            BINDING OF <3H>DIAZEPAM TO THE BENZDIAZEPINE
            RECEPTORS AND THEIR PSYCHOTROPIC PROPERTIES
 Abstract:
 CNR:
            5702423

 Author:
            Lyubimov, B. I.; Yavorskii, A. N.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 17, 5, 1983,
            378-380
 Title:
            LITHIUM HYDROXYBUTYRATE, A PREPARATION WITH
            PSYCHOTROPIC ACTIVITY
 Abstract:
 CNR:
            5702897

 Author:
            Khvostenko, O. G.; Khvostenko, V. I.; Ermakov, A. I.; Mosketi, K. V.;
            Shvedov, V. I.; et al.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 17, 10, 1983,
            738-744
 Title:
            INTERCONNECTION OF BIOLOGICAL ACTIVITY AND MOLECULAR
            STRUCTURE OF SOME PIPERAZINO<1,2-a>INDOLE
            DERIVATIVES, ANALOGS OF THE PSYCHOTROPIC
            PREPARATION PYRAZIDOLE
 Abstract:
 CNR:
            5703256

 Author:
            Mueller, Walter E.; Stillbauer, Angelika E.; El-Gamal, Safaa
 Reference:
            Journal, JPPMAB, J.Pharm.Pharmacol., EN, 35, 1983, 684-686
 Title:
            Psychotropic drug competition for <3H>imipramine binding further
            indicates the presence of only one high-affinity drug binding site on
            human a1-acid glycoprotein
 Abstract:
 CNR:
            5941387

 Author:
            Sindelar, Karel; Holubek, Jiri; Ryska, Miroslav; Svatek, Emil; Dlabac,
            Antonin; et al.
 Reference:
            Journal, CCCCAK, Collect.Czech.Chem.Commun., EN, 47, 1, 1982,
            72-87
 Title:
            TRICYCLIC PSYCHOTROPIC AGENTS CONTAINING TWO
            CHALCOGEN ATOMS IN THE CENTRAL RING: SYNTHESIS OF
            11-(DIMETHYLAMINOALKYL) DERIVATIVES OF
            11H-DIBENZO<b,e>-1,4-DIOXEPIN AND
            11H-DIBENZO<b,e>-1,4-DITHIEPIN
 Abstract:
            1-<2-(2-Fluorophenoxy)phenyl>-4-dimethylaminobutanol (XI) was
            synthesized from 2-(2-fluorophenoxy)benzoic acid (VIII) in three steps
            and cyclized with sodium hydride in dimethylformamide to the title
            compound V.Reaction of 5-chloro-2-(methylthio)thiophenol (XIV) with
            sodium and liquid ammonia afforded benzene-1,2-dithiol (XIII) which
            was treated with 2-bromobenzyl bromide and gave
            11H-dibenzo<b,e>-1,4-thiepin (II).An alternative synthesis of
            compound II consisted in the cyclization of
            2-(2-bromophenylthiomethyl)thiophenol (XVIII) and was accompanied
            by the simultaneous formation of 6H,12H-dibenzo<b,f>-1,5-dithiocin
            (XIX) and thianthrene (XX).Reaction of compound II with n-butyllithium
            and the following treatment with dimethylaminoalkyl chlorides or with
            carbon dioxide resulted on the one hand in two further title compounds
            VI and VII, and in the carboxylic acid XXI on the other.
            2-Chloro-11H-dibenzo<b,e>-1,4-dithiepin (XXII) was obtained by a
            further synthesis alternative using in the first step the cyclization of
            2-(4-chloro-2-chloromethylphenylthio)thiophenol (XXV).Compound VI
            and VII showed a high degree of activity in the test of antagonization of
            reserpine hypothermia in mice.
 CNR:
            5560456

 Author:
            Sindelar, Karel; Holubek, Jiri; Ryska, Miroslav; Dlabac, Antonin;
            Metysova, Jirina; et al.
 Reference:
            Journal, CCCCAK, Collect.Czech.Chem.Commun., EN, 47, 3, 1982,
            967-983
 Title:
            TRICYCLIC PSYCHOTROPIC AGENTS CONTAINING TWO
            CHALCOGEN ATOMS IN THE CENTRAL RING:DERIVATIVES OF
            11H-DIBENZ<b,f>-1,4-OXATHIEPIN
 Abstract:
            Reactions of 2-bromobenzyl bromide and its analogues XVII and XXV
            with 2-hydroxythiophenol resulted in 11H-dibenz<b,f>-1,4-oxathiepin
            (Ia) and its 2-chloro (Ib) and 2-trifluoromethyl derivative (Ic).Treatment
            of the lithium compounds derived from Ia and Ib with carbon dioxide
            and dimethylaminoalkyl chlorides gave compounds IIa, Va and VIab;
            modification of the side chains led to amines IVa, VIIa and VIIa.
            11-(1-Methyl-4-piperidyl) derivatives Xbc were obtained by chlorination
            of compounds Ibc with sulfuryl chloride or N-chlorosuccinimide and the
            following treatment with 1-methyl-4-piperidylmagnesium
            chloride.Compound Ib was transformed by oxidation to the sulfone XX
            affording by treatment with sodium hydride and
            tert-aminoalkylchlorides the basic sulfones XXI and XXII.While the
            nuclearly unsubstituted amines with the aliphatic side chains (IVa and
            VIIa) have intensive antireserpine activity and are potential
            antidepressants, the 11-(1-methyl-4-piperidyl) derivatives with a
            substituent in possition 2 of the skeleton (Xbc) are potential
            neuroleptics; the trifluoromethyl derivative Xc especially has
            outstanding cataleptic and antiapomorphine efficacy.
 CNR:
            5562899

 Author:
            Sindelar, Karel; Metysova, Jirina; Holubek, Jiri; Svatek, Emil; Protiva,
            Jiri; Protiva, Miroslav
 Reference:
            Journal, CCCCAK, Collect.Czech.Chem.Commun., EN, 47, 11, 1982,
            3077-3093
 Title:
            TRICYCLIC PSYCHOTROPIC AGENTS CONTAINING TWO
            CHALCOGEN ATOMS IN THE CENTRAL RING: 8-SUBSTITUTED
            6-(4-PIPERIDYL)-6H-DIBENZ<b,e>-1,4-OXATHIEPINS
 Abstract:
            2-(2-Fluorophenylthio)benzaldehydes IXa-c and
            5-chloro-2-(2-fluorophenylthio)acetophenone were treated with
            1-methyl-4-piperidylmagnesium chloride and
            3-dimethylaminopropylmagnesium chloride, respectively, and the
            resulting amino alcohols VIa-c, XVII and XVIII were cyclized with
            sodium hydride in dimethylformamide.In addition to the compounds
            Ia-c, XIX and XX, several types of by-products were
            obtained.Demethylation of compound Ib by the chloroformate method
            afforded the secondary amine IIb which was transformed to the amino
            alcohols IIIb and Vb.Compounds Ia-c are very potent neuroleptics with
            a high degree of central depressant and cataleptic activity.The amino
            alcohol Vb exhibits a very strong antiapomorphine effect in rats.
 CNR:
            5564534

 Author:
            Sindelar, Karel; Holubek, Jiri; Svatek, Emil; Ryska, Miroslav; Dlabac,
            Antonin; et al.
 Reference:
            Journal, CCCCAK, Collect.Czech.Chem.Commun., EN, 47, 11, 1982,
            3114-3133
 Title:
            TRICYCLIC PSYCHOTROPIC AGENTS CONTAINING TWO
            CHALCOGEN ATOMS IN THE CENTRAL RING:
            2-FLUORO-8-SUBSTITUTED
            6-(4-PIPERIDYL)-6H-DIBENZ<b,e>-1,4-OXATHIEPINS
 Abstract:
            The aldehydes VIa and VIb were transformed by treatment with
            chloroform and sodium hydroxide in the presence of
            triethylbenzylammonium chloride to the a-chloro acids VIIa and VIIb
            which were demethylated with boron tribromide and the products were
            cyclized with sodium hydroxide in dimethyl sulfoxide to
            2-fluoro-6H-dibenz<b,e>-1,4-oxathiepin-6-carboxylic acids Ia and
            Ib.Syntheses of the aldehydes XVIIbcd were carried out and the
            products treated with 1-methyl-4-piperidylmagnesium chloride to give
            the amino alcohols XVIbcd.Cyclization with sodium hydride in
            dimethylformamide afforded the title compounds XIIbcd; compounds
            XVIIIbc and XIX were isolated as by-products and
            characterized.Compound XIIb was transformed via the secondary
            amine XIIIb to the amino alcohol XIVb which was esterified to the
            decanoate XVb.Substances XIIbcd are highly active neuroleptic
            agents with an important prolongation of the central depressant
            effect.The decanoate XVb revealed the properties of a medium long
            acting depot neuroleptic.
 CNR:
            5564536

 Author:
            Protiva, Miroslav; Sedivy, Zdenek; Holubek, Jiri; Svatek, Emil;
            Metysova, Jirina; Bartosova, Marie
 Reference:
            Journal, CCCCAK, Collect.Czech.Chem.Commun., EN, 47, 11, 1982,
            3134-3147
 Title:
            POTENTIAL PSYCHOTROPIC AND ANTIHISTAMINE AGENTS: 1-
            AND 3-ALKYL-9-(3-DIMETHYLAMINOPROPYLIDENE)THIOXANTHENES
            AND 3-ALKYL-11-PIPERAZINO-10,11-DIHYDRODIBENZO<b,f>THIEPINS
 Abstract:
            Reactions of 3-methylthiophenol and 3-ethylthiophenol with
            2-iodobenzoic acid and (2-iodophenyl)acetic acid in the presence of
            potassium hydroxide and copper gave the acids IVab and Xab.The
            acids IVab afforded by cyclization with sulfuric acid mixtures of 1- and
            3-alkylthioxanthones (Va + VIa, Vb + VIb) which were separated by
            crystallization or chromatography and the individual compounds were
            identified by spectra.The slightly prevailing 3-alkyl derivatives Vab
            were reacted with 3-dimethylaminopropylmagnesium chloride to give
            the tertiary alcohols VIIab which were transformed by the acid
            catalyzed dehydration to the title compounds Iab. 1-Ethylthioxanthone
            (VIb) afforded similarly via the tertiary alcohol VIII the title compound
            IX.The acids Xab were cyclized with polyphosphoric acid
            unequivocally to the ketones XIab which were converted via the
            alcohols XIIab to the chloro derivatives XIIIab.Substitution reactions
            with 1-methylpiperazine and 1-(2-hydroxyethyl)piperazine led to the
            title compounds IIab and IIIb.The compounds prepared (I-III) have
            antihistamine activity and are more or less central
            depressant.Compounds Ib, IIb and IIIb revealed a clear cataleptic
            activity and compound Ib showed also antireserpine
            activity.Compound IX is centrally depressant only in high doses but it
            has anticonvulsant effects and a significant antitussive effect.
 CNR:
            5564537

 Author:
            Sindelar, Karel; Holoubek, Jiri; Svatek, Emil; Ryska, Miroslav; Dlabac,
            Antonin; Protiva, Miroslav
 Reference:
            Journal, CCCCAK, Collect.Czech.Chem.Commun., EN, 47, 5, 1982,
            1367-1381
 Title:
            TRICYCLIC PSYCHOTROPIC AGENTS CONTAINING TWO
            CHALCOGEN ATOMS IN THE CENTRAL RING: SYNTHESIS OF
            6-(AMINOALKYL) DERIVATIVES OF
            6H-DIBENZ<b,e>-1,4-OXATHIEPIN
 Abstract:
            Heating of 2-(2-hydroxyphenylthio)benzoic acid (XX) with acetic
            anhydride gave dibenz<b,e>-1,4-oxathiepin-6-one
            (XXII).Demethylation of 2-(2-methoxyphenylthio)benzyl bromide (XI)
            with boron tribromide and the following treatment with aqueous
            sodium hydroxide in dimethyl sulfoxide afforded
            6H-dibenz<b,e>-1,4-oxathiepin (I) which was halogenated with
            chlorine or N-bromosuccinimide only to the undesirable 2-halogeno
            derivatives II and III.A reaction of
            2-(2-methoxyphenylthio)benzaldehyde (XII) with chloroform and
            50percent aqueous sodium hydroxide in the presence of
            triethylbenzylammonium chloride led to the a-chloro acid XIX whose
            demethylation with boron tribromide and the following cyclization with
            sodium hydroxide in dimethyl sulfoxide gave a mixture with prevailing
            6H-dibenz<b,e>-1,4-oxathiepin-6-carboxylic acid (IV).Amino alcohols
            XXV - XXVIII were obtained by reactions of
            2-(2-fluorophenylthio)benzaldehyde (XXIV) with the corresponding
            Grignard reagents and the products were cyclized with sodium hydride
            in dimethylformamide to the title compounds V-VIII.While compounds
            V and VI showed antireserpine effects and can be considered as
            potential antidepresants, compound VIII has a strong central
            depressant activity, brings about ataxia, hypothermia and potentiates
            the cataleptic action of neuroleptics (properties of a tranquillizer).
 CNR:
            5567878

 Author:
            Agarwal, Rajesh; Chaudhary, Chapla; Misra, V. S.
 Reference:
            Journal, IJSBDB, Indian J.Chem.Sect.B, EN, 21, 12, 1982, 1110-1113
 Title:
            Synthesis and CNS Activity of 4-Arylideneamino-N,N-diphenylbenzamides,
            1-<p-(N,N-Diphenylcarbamoyl)phenyl>-3-(p-substituted phenyl)thioureas and
            6-Substituted
            3-<N-(3H-2-Methyl-4-oxo-3-quinazolylamino)methyl>2-oxo/thio-benzoxazoles
 Abstract:
            4-Arylideneamino-N,N-diphenylbenzamides (IIIa-h),
            1-<p-(N,N-diphenylcarbamoyl)phenyl>-3-(p-substituted phenyl)thioureas (IVa-d)
            and 6-substituted
            3-<N-(3H-2-methyl-4-oxo-3-quinazolylamino)methyl>-2-oxo-/thio-benzoxazoles
            (Va-d) have been synthesized from 4-amino-N,N-diphenylbenzamide
            (IIa).Similarly thioureas IVe-h and benzoxazoles Ve-h have been prepared from
            2-aminoquinazolin-4(3H)-one (IIb).Compounds III, IV and V are found to be
            psychotropic and nontoxic.
 CNR:
            5577480

 Author:
            Michel, A.; Gustin, R.; Evrard, G.; Durant, F.
 Reference:
            Journal, BSCBAG, Bull.Soc.Chim.Belg., FR, 91, 1, 1982, 123-130
 Title:
            ETUDE STRUCTURALE DES ANALOGUES DE LA MINAPRINE: 2.
            STRUCTURE CRISTALLINE DU DICHLORHYDRATE DE
            L'ANALOGUE 4-PHENYLE
 Abstract:
            This study is part of a more general investigation about conformations
            of morpholinoethylamino pyridazines.Some of these molecules exhibit
            psychotropic activity related with the substitution on the pyridazine
            ring.The molecular structure of the title compound analyzed by X-Ray
            diffraction is discussed in terms of electronic delocalization into the
            pyridazine ring.
 CNR:
            5608054

 Author:
            Michel, A.; Gustin, R.; Evrard, G.; Durant, F.
 Reference:
            Journal, BSCBAG, Bull.Soc.Chim.Belg., FR, 91, 1, 1982, 49-56
 Title:
            ETUDE STRUCTURALE DES ANALOGUES DE LA MINAPRINE: 1.
            STRUCTURE MOLECULAIRE DU DICHLORHYDRATE DE LA
            DESMETHYLMINAPRINE
 Abstract:
            This paper initiates a series of structural studies on analogs of
            minaprine, a psychotropic drug, in order to establish structure-activity
            relationships.The results of the crystal structure analysis of the
            desmethylminaprine.2 HCl.H2O are related.In particular, we discuss
            the electronic delocalization in the aminopyridazinium moiety.
 CNR:
            5608284

 Author:
            Matsuo, Masaaki; Taniguchi, Kiyoshi; Ueda, Ikuo
 Reference:
            Journal, CPBTAL, Chem.Pharm.Bull., EN, 30, 4, 1982, 1141-1150
 Title:
            NEUROTROPIC AND PSYCHOTROPIC AGENTS. IV. SYNTHESIS AND PHARMACOLOGICAL
            PROPERTIES OF
            7-CHLORO-5-(2-CHLOROPHENYL)-2-(2-DIMETHYLAMINOETHYLTHIO)-3H-1,4-BENZODIAZEPINE
            AND RELATED COMPOUNDS
 Abstract:
            The synthesis and pharmacological properties of
            7-chloro-5-(2-chlorophenyl)-2-(2-dimethylaminoethylthio)-3H-1,4-benzodiazepine (III-1) and related
            compounds are described.Compound III-1 was prepared from the thiolactam (II-1) by treatment with
            2-dimethylaminoethyl chloride in the presence of base in aqueous methanol and
            7-chloro-5-(2-chlorophenyl)-2-methoxy-3H-1,4-benzodiazepine (IV) was obtained as a by-product.The
            latter (IV) was hydrolyzed in acid medium to give methyl
            (E)-<2-amino-5-chloro-a-(2-chlorophenyl)benzylidene>aminoacetate (syn-form) (XIX), which was
            converted into the 1,4-benzodiazepine (I-1) by further acid treatment.Compound XIX isomerized to the
            corresponding anti-form (XXII) on heating.Most of the compounds prepared had an effect similar to that
            of diazepam in causing taming and anticonvulsant effects in mice.Keywords---2-substituted
            thio-3H-1,4-benzodiazepine; 2-alkoxy-3H-1,4-benzodiazepine;
            1,3-dihydro-2H-1,4-benzodiazepine-2-thione; hydrolysis of lactam ether; syn-anti-isomer of ketimine:
            pharmacological test; taming effect in mice: anticonvulsant effect in mice
 CNR:
            5667969

 Author:
            Bermann, Marie-Christine; Bonte, Jean-Paul; Lesieur-Demarquilly,
            Isabelle; Debaert, Michel; Lesieur, Daniel
 Reference:
            Journal, EJMCA5, Eur.J.Med.Chem.Chim.Ther., FR, 17, 1, 1982,
            85-88
 Title:
            PHARMACOMODULATION DU MODELE BENZOXAZOLINONE PAR
            LA STRUCTURE ARYL-PIPERAZINIQUE
 Abstract:
            The synthesis of various 3-(4-aryl 1-piperazinyl-1) alkyl
            benzoxazolinones is described.All these compounds were tested for
            analgesic and psychotropic activities.One of them showed very
            interesting analgesic activity
 CNR:
            5677973

 Author:
            Watanabe, Takao; Matsuo, Masaaki; Taniguchi, Kiyoshi; Ueda, Ikuo
 Reference:
            Journal, CPBTAL, Chem.Pharm.Bull., EN, 30, 4, 1982, 1473-1476
 Title:
            Neurotropic and Psychotropic Agents. V. An Improved Synthesis of
            7-Chloro-5-(2-chlorophenyl)-2-(2-dimethylaminoethylthio)-3H-1,4-benzodiazepine
            and Related Compounds
 Abstract:
            An improved method for the synthesis of
            7-chloro-5-(2-chlorophenyl)-2-(2-dimethylaminoethylthio)-3H-1,4-benzodiazepine
            (IIa) and related compounds is described.IIa was obtained in 75.1 percent yield by
            the reaction of the 1,4-benzodiazepin-2-one (Ia) with 2-dimethylaminoethanethiol
            in the presence of titanium tetrachloride; a small amount of
            7-chloro-5-(2-chlorophenyl)-2-dimethylamino-3H-1,4-benzodiazepine (III) was
            obtained as a byproduct.A mechanistic interpretation of the formation of III is
            presented.Keywords: 2-substitueted thio-3H-1,4-benzodiazepine; Lewis acids;
            titaniumtetrachloride; dialkylaminoalkanethiol; dimethylamine
 CNR:
            5682431

 Author:
            Kishimoto, Teiji; Matsuo, Masaaki; Ueda, Ikuo
 Reference:
            Journal, CPBTAL, Chem.Pharm.Bull., EN, 30, 4, 1982, 1477-1480
 Title:
            Neurotropic and Psychotropic Agents. VI.
            1-Alkoxymethyl-1,3-dihydro-2H-1,4-benzodiazepin-2-ones
 Abstract:
            1-Alkoxymethyl-1,3-dihydro-2H-1,4-benzodiazepin-2-ones (II) were
            prepared by two methods: one was direct alkylation of
            1,4-benzodiazepin-2-ones (I) with alkoxymethyl chlorides and the other
            was via 2-<N-(alkoxymethyl)phtalimidoacetamido>benzophenones (IV)
            which were prepared from the corresponding
            2-(phtalimidoactamido)benzophenones (III) and alkoxymethyl
            chlorides.Certain compounds prepared had comparable activity to
            diazepam and chlorodiazepoxide in taming and anticonvulsant tests in
            mice. hydrolysis of
            3-<N-acyl-p-methylphenylamino>-1-<p-methylphenylamino>-2-butene
            <VI> were examined.
 CNR:
            5682432

 Author:
            Matsuo, Masaaki; Taniguchi, Kiyoshi; Ueda, Ikuo
 Reference:
            Journal, CPBTAL, Chem.Pharm.Bull., EN, 30, 4, 1982, 1481-1484
 Title:
            Neurotropic and Psychotropic Agents. VII. Synthesis and
            Pharmacological Properties of
            2-(Alkoxyalkilamino)-3H-1,4-benzodiazepines
 Abstract:
            The synthesis and pharmacological properties of some
            2-(alkoxyalkilamino)-3H-1,4-benzodiazepine derivatives (I and II) are
            described.Compounds I were prepared from the corresponding
            2-methylthio-1,4-benzodiazepines and primary amines.Compounds II
            were prepared by alkylation of the corresponding
            2-monoalkylamino-1,4-benzodiazepines with alkyl or alkoxyalkyl
            halides.The compounds (I and II) showed tranquilizing profiles like that
            of chlorodiazepoxide in taming and anticonvulsant tests in mice.
            Keywords: 2-(alkoxyalkylamino)-3H-1,4-benzodiazepine;
            2-monoalkylamino-3H-1,4-benzodiazepine; pharmacological test;
            taming effect in mice; anticonvulsant effect in mice
 CNR:
            5682433

 Author:
            Drake, J. A. G.; Jones, D. W.
 Reference:
            Journal, ACBCAR, Acta Crystallogr.Sect.B, EN, 38, 1982, 200-203
 Title:
            The Structure of Dibenz<b,f>oxepin
 Abstract:
            The structure of dibenz<b,f>oxepin, C14H10O, parent molecule of a
            group of psychotropic drugs, has been determined by direct methods
            from 776 X-ray diffractometer data and refined by least squares to a
            final residual R of 0.115.The space group is orthorhombic, Pnam, with
            a = 8.236(3), b = 6.115(1), c = 19.667(4) Angstroem; Z = 4, V = 990.3
            Angstroem3; Dm = 1.30(1), Dc = 1.29 Mg m-3.The molecules, located
            on mirror planes passing through the O atom and the midpoint of the
            1.327(6) Angstroem C(10)-C(11) ethylenic bond, have almost planar
            benzene rings mutually inclined at a comparatively small dihedral
            angle of 134(2)o.The heterocyclic ring, in boat conformation, has a
            C-O-C bond angle of 115.7(4)o and C-O bonds of 1.390(5) Angstroem.
 CNR:
            5683532

 Author:
            Sato, Makoto; Arimoto, Masahiro
 Reference:
            Journal, CPBTAL, Chem.Pharm.Bull., EN, 30, 2, 1982, 719-722
 Title:
            Psychotropic Agents. VI. An Improved Synthetic Method for
            4'-Fluoro-4-<4-(2-thioxo-1-benzimidazolinyl)piperidino>butyrophenone
 Abstract:
            The title compound (8) was prepared by two improved
            methods.Initially, the 4-aminopiperidine derivative (11) was prepared
            by treatment of 4-aminopyridine (9) with the aralkyl chloride (5),
            followed by NaBH4 reduction of the resulting 4-amonopyridinium salt
            (10).Reaction of 11 with 2-chloronitrobenzene gave the intermediate
            (6).Subsequently, the key intermediate (7) was similarly prepared
            starting from 4-chloropyridine (12) via the pyridinium salt (14).In this
            method the target compound (8) was prepared in good yield with the
            technical advantage that the four steps (13->14->7->8) could be
            conveniently carried out in a one-pot procedure.
 CNR:
            5683969

 Author:
            Hoffmeister, F.; Benz, U.; Heise, H.; Krause, H. P.; Neuser, V.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 32, 4, 1982, 347-360
 Title:
            Behavioral Effects of Nimodipine in Animals
 Abstract:
            Neuro- and psychopharmacological effects of
            isopropyl-(2-methoxy-ethyl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate
            (Bay e 9736, nimodipine) are described using a variety of methods measuring behavior under
            normal conditions, under the influence of psychotropic drugs, as well as under the influence of
            ischemia or hypoxia.It has been demonstrated that nimodipine - although not being very potent
            when measured in mg/kg - exerts neuro- and psychopharmacological effects characterized by
            influences on the extrapyramidal system, aggresive defensive behavior, and chemically induced
            seizures.Electroencephalographical changes become evident whenever the normal equilibrium
            between cerebral catecholamine and cerebral serotonin levels is disturbed.When measured
            under the contingencies of a one trial passive avoidance paradigm, nimodipine is able to prevent
            the occurrence of retrograde amnesia in rodents after amnesiogenic events such as maximal
            electroconvulsive seizure or hypoxia.The subtance prevents behavioral and
            electroencephalographic disturbances, elicited by a total cerebral ischemia, which is lethal in
            non-treated cats.It is concluded that nimodipine besides being a cerebrally vasoactive agent has
            psychopharmacological properties with a profile af actions hitherto unknown. - Key words:
            Amnesia .Bay e 9736.Ca-antagonists .Nimodipine, pharmacology .Vasodilators, cerebral
 CNR:
            5734231

 Author:
            Biziere, K.; Kan, J. P.; Souilhac, J.; Muyard, J. P.; Roncucci, R.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 32, 8, 1982, 824-831
 Title:
            Pharmacological Evaluation of Minaprine Dihydrochloride, a New
            Psychotropic Drug
 Abstract:
            Minaprine
            (3-<2-morpholino-ethylamino>-4-methyl-6-phenyl-pyridazine
            dihydrochloride; 30038CM; trade name in France: Cantor) is a new
            psychotropic drug.The therapeutic profile of minaprine differs from that
            of other known psychotropic agents; in man the drug antagonizes the
            "inhibitory syndrome" characterized by decreased spontaneous
            activity, reduction in basic drives, slowed thoughts, feelings of
            tiredness and social withdrawal.Preliminary clinical trials have
            indicated that minaprine may also be effective in certain depressive
            states.This finding prompted us to study the effects of minaprine in
            animal models for depression.Like most antidepressants minaprine
            antagonizes behavioral despair, but the effect exhibits a slow onset
            and maximal activity is reached 24 h after administration.Minaprine
            also antagonizes reserpine-induced ptosis, this effect has a rapid
            onset, and is long-lasting.In contrast, minaprine poorly antagonizes
            reserpine-induced hypothermia.Unlike most antidepressants
            minaprine does not potentiate yohimbine-induced lethality.Minaprine
            potently antagonizes prochlorperazine-induced catalepsy in rats and
            potentiates amphetamine-induced stereotyped behavior, suggesting
            that the drug may enhance dopaminergic transmission.Finally,
            minaprine does not antagonize either oxotremorine-induced tremors or
            physiostigmine-induced lethality.Taken together the results of the
            present study indicate that minaprine is active on certain, but not all,
            animal models for depression and suggest the drug may have a
            potential clinical utility in the treatment of human depressions. - Key
            words: Antidepressants .Cantor .Imipramine, pharmacology
            .Minaprine, pharmacology .Psychotropic drugs
 CNR:
            5734268

 Author:
            Wagner, Edwin
 Reference:
            Journal, PJCHDQ, Pol.J.Chem., EN, 56, 1, 1982, 131-139
 Title:
            SYNTHESIS AND HYDRATION OF DERIVATIVES OF
            3-ALLYL-3H<1,5>BENZODIAZEPINE-2,4-DIONES
 Abstract:
            Hydration of derivatives of 3-allyl-3H<1,5>benzodiazepine-2,4-diones
            (3a-g) and 5,5-diallyl- and 5-allyl-5-phenylbarbituric acids with
            100percent H2SO4 yields compounds 4a-g, 11a, b, c and 13a, b and
            15a, b.Some data indicate formation of cation 8 as an intermediate.A
            series of new compounds, particularly 3g, showed a psychotropic
            activity.
 CNR:
            5745513

 Author:
            Gessner, B.; Klasser, M.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., GE, 32, 5, 1982, 579-583
 Title:
            Influence of a Pentifylline-Nicotinic Acid Combination on Vigilance and
            Mental Performance
 Abstract:
            The effect of a single dose of 4 sugar-coated tablets of Cosaldon
            (1-hexyl-3,7-dimethylxanthine (pentifylline) + nicotinic acid) was shown
            by quantitative pharmaco-EEG investigations and psychometric tests
            in 12 volunteers aged 58 to 75 years, who were in a good physical
            condition.The design was randomized, double-blind and cross-over
            designed against placebo.EEG and psychometric tests were made
            before medication and repeated each hour up to 6 h after
            medication.Each turn was split up into a resting-EEG (R-EEG) and a
            vigilance-EEG (V-EEG) lasting 3 min each; the psychometric tests
            were made immediately afterwards.An increase of the vigilance,
            shown by an increased EEG-power, was found after Cosaldon
            administration as compared to placebo.Furtermore, the delta and theta
            intensity decreased to a statistically significant degree, while the
            intensity within the alpha-1-scope increased.The strongest effect as
            compared to placebo could be observed 4 h after medication.The
            statistical significance was shown for the V-EEG-condition, the R-EEG
            showed only minor changes.The effects in the occipital region were
            stronger than in the more frontal parts.In accordance with the results of
            the EEG, the psychological tests showed remarkable improvements in
            performances which reached their maximum between 2 and 4 h after
            medication. - Key words: Cosaldon; Nicotinic acid, combination with
            pentifylline, encephalotropic, pharmacodynamic, psychotropic
            properties; Pentifylline, combination with nicotinic acid,
            encephalotropic, pharmacodynamic, psychotropic properties
 CNR:
            5795043

 Author:
            Silvestrini, B.; Lisciani, R.; Baldini, A.; Sanctis, A. J.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 32, 6, 1982, 668-673
 Title:
            Psychocharmacological Profile of Dapiprazole, a New Potential Antipsychotic Agent
 Abstract:
            3-<2-<4-(2-Methylphenyl)-1-piperazinyl>ethyl>-5,6,7,8-tetrahydro-1,2,4-triazolo<4,3-a>pyridine
            HCl (dapiprazole) is a new compound endowed with a unique psyvhopharmacological
            profile.It inhibits amphetamine toxicity in grouped mice, and alcohol and morphine withdrawal
            syndromes, whereas it is almost inactive in the screening models for neuroleptics relying on
            dopaminergic acitivty.It also produces sedation, blocks conditioned avoidance reflex, reduces
            the response to noxious stimuli, has EEG synchronizing effects and inhibits the arousal
            reaction.Dapiprazole is a potent central and peripheral adrenolytic agent.Its acute toxicity is
            low.On the basis of these data, clinical investigations of dapiprazole are suggested in
            psychotic conditions such as the withdrawal syndromes, schizophrenia and schizoaffective
            disorders. - Key words: a-Adrenergic blocking agents; Dapiprazole, psychopharmacology;
            Psychotropic agents
 CNR:
            5795059

 Author:
            Lisciani, R.; Baldini, A.; Silvestrini, B.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 32, 6, 1982, 674-678
 Title:
            General Pharmacological Properties of Dapiprazole, a Potential Psychotropic Agent
 Abstract:
            A study of the general pharmacology of
            3-<2-<4-(2-methylphenyl)-1-piperazinyl>ethyl>-5,6,7,8-tetrahydro-1,2,4-triazolo-<4,3-a>pyridine
            HCl(dapiprazole), a new psychotropic agent, is reported.The predominant feature of this
            compund appears to be a-adrenergic blockade.This action has been observed both in vitro and
            in vivo.Dapiprazole also possesses antihistaminic and antiserotonin activities, although at
            relatively high doses.The antihistaminic action appears to be restricted to H1 receptors as
            sugggested by the lack of activity on the guinea-pig atrium.Dapiprazole appears to be avoid of
            anticholinergic, local anaesthetic, antimicrobial and diuretic effects. - Key words: a-Adrenergic
            blocking agents; Dapiprazole, general pharmacology; Psychotropic agents
 CNR:
            5795060

 Author:
            Silvestrini, B.; Bonomi, L.; Lisciani, R.; Perfetti, S.; Belluci, R.; et al.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 32, 6, 1982, 678-681
 Title:
            Effects of Dapiprazole on Pupillary Size and Intraocular Pressure in Rabbits
 Abstract:
            The effects of
            3-<2-<4-(2-methylphenyl)-1-piperazinyl>ethyl>-5,6,7,8-tetrahydro-1,2,4-triazolo<4,3-a>pyridine
            HCl (dapiprazole), a new drug with a-adrenergic blocking properties, on pupillary diameter and
            intraocular pressure have been studied in rabbits.Following i. v. administration, a reduction of
            intraocular pressure is observed at doses devoid of activity on pupillary diameter.Following
            topical application, a miotic and ocular hypertensive action was observed at the same doses;
            the hypotensive action is produced in both normal rabbits and in rabbits with water load- or
            corticosteroid-induced ocular hypertension.Contact lenses increase the duration of effects of
            dapiprazole.These results suggest a potential interest of dapiprazole in glaucoma, with
            particular reference to the topical treatment of angleclosure glaucoma. - Key words:
            a-Adrenergic blocking agents; Dapiprazole, intraocular pressure, pupillary size; Psychotropic
            agents
 CNR:
            5795061

 Author:
            Hoo, J. J.; Noldt, P.; Beckermann, W. J.; Agarwal, D. P.; Goedde, H. W.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 32, 6, 1982, 681-683
 Title:
            In vitro Effect of Haloperidol, Chlorpromazine, Imipramine and Lithium
            on the Erythrocyte Catechol-O-methyltransferase
 Abstract:
            Haloperidol, chlorpromazine, imipramine and lithium in concentrations
            similar to the average therapeutic plasma levels did not exert any in
            vitro inhibition on the erythrocyte catechol-O-methyltransferase
            (COMT).The inhibitory effects of haloperidol, chlorpromazine and
            imipramine were noted first at concentrations 1000-10000 times their
            respective average therapeutic plasma levels.Unlike the former three
            psychotropic drugs, lithium exerted an in vitro inhibition already at a
            concentration 40 times the average therapeutic plasma level and that
            in a competitive way.The inhibitory effect of lithium could be
            neutralized by increasing the magnesium concentration, like-wise in a
            competitive way. - Key words: Catechol-O-methyltransferase;
            Chlorpromazine; Haloperidol; Imipramine; Lithium; Psychotropic drugs
 CNR:
            5795062

 Author:
            Kolasa, K.; Fusi, R.; Garattini, S.; Consolo, S.; Ladinsky, H.
 Reference:
            Journal, JPPMAB, J.Pharm.Pharmacol., EN, 34, 1982, 314-317
 Title:
            Neurochemical effects of buspirone, a novel psychotropic drug, on the
            central cholinergic system
 Abstract:
            Buspirone, a novel psychotropic anxioselective agent, produced a
            dose-dependent decrease in the level of acetylcholine in the striatum
            of rat.The maximum effect of about 25-30percent was produced at the
            dose of 20 mg kg-1.A smaller decrease of 10percent was also found in
            the n.accumbens-olfactory tubercle while other brain regions were
            unaffected.The drug did not alter striatal choline acetyltransferase or
            acetylcholinesterase activities and was feeble in displacing
            <(3)H>dexetimide from its specific muscarinic binding sites.The effect
            of buspirone in lowering acetylcholine content was more marked and
            longer lasting in the striatum of female than male rats.Buspirone
            proved to be weak as a blocker of the dopamine receptor agonist,
            apomorphine, and it appears that only a small proportion of the
            decrease in striatal acetylcholine concent can be attributed to the
            blockade of dopamine receptors.Rapid homologous tolerance to an
            acute challenge with buspirone on striatal acetylcholine was achieved
            within seven days of its chronic administration, and, unlike clozapine, a
            cross tolerance of buspirone to chronic haloperidol treatment was also
            observed.Other data indicating that the drug differed from haloperidol
            both qualitatively and quantitatively on dopaminergic neurochemical
            parameters, and the fact that it is not cataleptogenic, suggest that
            buspirone cannot be considered a typical neuroleptic agent.The
            possibility that buspirone may act as an agonist at certain presynaptic
            dopamine receptors, which could translate into a fall in striatal
            acetylcholine content, is discussed.
 CNR:
            5806016

 Author:
            Fong, M. H.; Garattini, S.; Caccia, S.
 Reference:
            Journal, JPPMAB, J.Pharm.Pharmacol., EN, 34, 1982, 674-675
 Title:
            1-m-Chlorophenylpiperazine is an active metabolite common to the
            psychotropic drugs trazodone, etoperidone and mepiprazole
 Abstract:
 CNR:
            5807905

 Author:
            Ong, Helen H.; Agnew, Marc N.
 Reference:
            Journal, JHTCAD, J.Heterocycl.Chem., EN, 18, 1981, 815-820
 Title:
            Novel Tetracyclic Spiropiperidines. II. Synthesis of
            2-Aryl-2,3-dihydrospiro<benzofuran-3,4'-piperidines>
 Abstract:
            A series of 2-aryl-2,3-dihydrospiro<benzofuran-3,4'-piperidines> has
            been synthesized as potential psychotropic agents via an efficient
            intramolecular fluorine displacement reaction.Treatment of a key
            intermediate, 4-cyano-4-(2-fluorophenyl)-1-methylpiperidine (2), with a
            large excess of phenylmagnesium bromide in refluxing tetrahydrofuran
            led to some 2-arylspiro<3H-indole-3,4'-piperidine> derivatives, 10 and
            11, whose structures are elucidated on the basis of chemical and
            spectral evidence.
 CNR:
            5560900

 Author:
            Okafor, Charles O.
 Reference:
            Journal, JHTCAD, J.Heterocycl.Chem., EN, 18, 1981, 1445-1449
 Title:
            Studies in the Heterocyclic Series. XX. 1,4-Diazaphenoxazine and
            Related Compounds
 Abstract:
            As part of our program on the synthesis of new psychotropic agents,
            the parent rings of two diazaphenoxazines are described.The reaction
            of 2-aminophenol and 2,3-dichloropyrazine in alkaline media gave
            good yields of 1,4-diazaphenoxazine.Replacement of
            2,3-dichloropyrazine with 2,3-dichloroquinoxaline gave on the other
            hand the heterocycle, 1,4-diazabenzo<b>phenoxazine.Nitration and
            S-oxide formation were achieved by reaction with mixed nitric and
            sulfuric acids.Mechanistic pathways to these compounds were also
            discussed.
 CNR:
            5561532

 Author:
            Nodiff, E. A.; Sharma, H. L.; Taunk, P. C.; Shukla, A. P.; Sadhnani, M.
            D.; et al.
 Reference:
            Journal, JHTCAD, J.Heterocycl.Chem., EN, 18, 1981, 1529-1532
 Title:
            Syntheses of Some Hydroxylated Metabolites of Psychotropic
            Trifluoromethyl Analogs of Chlorpromazine
 Abstract:
            The syntheses of 7-hydroxy derivatives of trifluoperazine,
            nor1-trifluoperazine, fluphenazine, triflupromazine and
            nor1-triflupromazine are described.These were prepared as analytical
            standards for the identification of these metabolites in biological
            materials.
 CNR:
            5567553

 Author:
            Wiese, Dietmar; Tacke, Reinhold; Wannagat, Ulrich
 Reference:
            Journal, LACHDL, Liebigs Ann.Chem., GE, 7, 1981, 1285-1293
 Title:
            Sila-Pharmaca, 23. -
            9,9-Dimethyl-10-(3-dimethylaminopropyl)-9-silaacridane, a
            Sila-Analogue of Dimetacrine, and Structurally Related Compounds
 Abstract:
            Sila-dimetacrine (3a), a sila-analogue of the psychotropic drug
            dimetacrine (2), and its N,N-dimethyl derivative 3b as well as its
            3-chloro derivative 3c were synthesized from o-haloanilines 4a-c via
            the - partially unknown - intermediates 5a-c to 10a-d.Their properties
            are described and their structure is confirmed by elemental analysis,
            1H-NMR, and mass spectroscopy.The preparation of the intermediate
            bis(2-bromophenyl)amine (9a) could be improved.
 CNR:
            5624008

 Author:
            Domelsmith, L. N.; Eaton, Thomas A.; Houk, K. N.; Anderson, G. M.;
            Glennon, R. A.; et al.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 24, 12, 1981, 1414-1421
 Title:
            Photoelectron Spectra of Psychotropic Drugs. 6. Relationships
            between Physical Properties and Pharmacological Actions of
            Amphetamine Analogues
 Abstract:
            The valence ionization potentials of seven additional members of a
            series of 2,4,5-trisubstituted amphetamines
            (1-phenyl-2-aminopropanes) were measured by UV photoelectron
            spectroscopy.These and previously published data provide
            experimental measures of the gross electron-donor ability of the
            aromatic rings of 23 amphetamines.Analogues bearing the
            2,5-dimethoxy orientation were found to possess the lowest ionization
            potentials (IPs); for the analogously X-substituted compounds, the IPs
            increased in the order 2,5-(OMe)2-4-X < 2,4-(OMe)2-5-X <
            4,5-(OMe)2-2-X.Relationships between human psychotomimetic
            activity (MU), rabbit hyperthermia (SRU), serotonergic receptor affinity
            (pA2), and charge-transfer complex stabilities (KDNB) were evaluated
            statistically.A good correlation (r2 = 0.92) was established between the
            human and rabbit potencies, but poorer correlations were obtained
            between animal potencies and pA2's (r2 = 0.68-0.69) or KDNB's (r2 =
            0.03!).Analyses of the regression relationships between these
            pharmacological measures and two physical properties, IP and lipid
            solubility (as modeled by log P), were explored.In general, greater
            potency is associated with decreasing IP and increasing log
            P.However, numerous exceptions to single parameter regressions are
            found.The unusually great potency of the 2,5-(OMe)2-4-X analogues,
            while qualitatively related to the physical properties, is quantitatively
            underestimated by these predictors.However, inclusion of a parameter
            (p4) which explicitly acknowledges the type of the 4-substituent leads
            to much improved correlations.These results support previous
            suggestions that 4-substituents interact directly with the receptor.
 CNR:
            5638077

 Author:
            Lukevits, E.; Germane, S.; Erchak, N. P.; Pudova, O. A.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 15, 4, 1981,
            257-260
 Title:
            HETEROORGANIC DERIVATIVES OF FURAN. XXVI. SYNTHESIS
            AND PSYCHOTROPIC PROPERTIES OF HYDROCHLORIDES OF
            FURYL- AND THIENYL-CONTAINING AMINOALKYLSILANES
 Abstract:
 CNR:
            5641471

 Author:
            Praliev, K. D.; Sydykov, B. T.; Sokolov, D. V.; Kurilenko, V. M.;
            Khlienko, Zh. N.; Moiseeva, L. M.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 15, 1, 1981,
            20-22
 Title:
            SYNTHESIS OF DERIVATIVES OF PIPERIDINE AND
            DECAHYDROQUINOLINE, THEIR ANALGESIC AND
            PSYCHOTROPIC PROPERTIES. X. MONO- AND BICYCLIC
            ANALOGS OF PRODINE
 Abstract:
 CNR:
            5642199

 Author:
            Sozinov, V. N.; Orlova, L. M.; Mashkovskii, M. D.; Suvorov, N. N.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 15, 6, 1981,
            412-415
 Title:
            INVESTIGATION OF THE PSYCHOTROPIC ACTIVITY OF
            3-tert-BUTYLAMINOACYLINDOLES
 Abstract:
 CNR:
            5642211

 Author:
            Reboul, J. P.; Cristau, B.; Pepe, G.
 Reference:
            Journal, ACBCAR, Acta Crystallogr.Sect.B, FR, 37, 1981, 394-398
 Title:
            Structure du Dihydro-10,11 5H-Dibenzo<a,d>cycloheptene. Support
            Tricyclique d'Analogues Structuraux des Antidepresseurs
            Imipraminiques
 Abstract:
            As part of an investigation of tricyclic compounds and related
            psychotropic molecules, the structure of 10,11
            dihydro-5H-dibenzo<a,d>cycloheptene (C15H14, Mr=194.58) is
            reported.This study was undertaken to analyse the modifications
            induced when the N atom of iminobenzyl is replaced by a C
            atom.Crystals are monoclinic, P21/c, with a=11.645(3), b=6.436(2),
            c=17.246(5) Angstroem, b=122.76(3) deg, V=1087.0 Angstroem3, Z=4,
            Dc=1.18, Dm=1.19(2) Mg m-3, F(000)=416, m(Cu Ka)=0.43 mm-1.The
            structure was determined by multisolution direct methods and refined
            by full-matrix least squares to an R of 0.044 for 820 independently
            measured reflexions.The dihedral angle between the two planes of the
            benzene rings is 123.1(2) deg.
 CNR:
            5665897

 Author:
            Sato, Makoto; Uchimaru, Fumihiko
 Reference:
            Journal, CPBTAL, Chem.Pharm.Bull., EN, 29, 11, 1981, 3134-3144
 Title:
            Psychotropic Agents V. Synthesis of 1,3-Diphenyl-4-(4-substituted
            piperidinyl)-1-butanones and related compounds.
 Abstract:
            A series of 1,3-diphenyl-1-butanone derivatives (11-14) was
            synthesized as a part of a search for new psychotropic agents.In the
            reaction of 4-chloro-1,3-diphenyl-1-butanones (8a,d) with piperidine
            derivatives (10,15), rearranged products (16-18) were obtained
            together with 1,3-diphenyl-1-butanone derivatives (11,14,20).A reaction
            mechanism involving the cyclisation of 8a,d to cyclopropane
            derivatives (22a,d) and subsequent addition reaction with piperidine
            derivatives (10,15) to 22a,d is proposed.Keywords - butyrophenone;
            neuroleptic activity; 1,3-diphenyl-1-butanone derivatives;
            1,4-diphenyl-1-butanone derivatives; rearrangement
 CNR:
            5675759

 Author:
            Sato, Makoto; Kosasayama, Akira; Uchimaru, Fumihiko
 Reference:
            Journal, CPBTAL, Chem.Pharm.Bull., EN, 29, 10, 1981, 2885-2892
 Title:
            Psychotropic Agents IV. Syntheses of b-Phenyl-g-butyrolactone
            Derivatives
 Abstract:
            b-Phenyl-g-butyrolactones (IIIa-j) bearing several substituents on the
            phenyl ring were synthesized.Deamination of
            4-amino-3-(2,4,6-trimethylphenyl)butyric acid (IV) with nitrous acid
            gave rearranged compounds, b-(2,4,6-trimethylbenzyl)-b-propiolactone
            (V) and 3-hydroxy-4-(2,4,6-trimethylphenyl)butyric acid (VI) together
            with the required b-(2,4,6-trimethylphenyl)-g-butyrolactone
            (IIIj).Reaction of 2-phenyloxirane derivatives (IXh-j) with sodium
            diethylmalonate was found to be a convenient method for the
            preparation of b-phenyl-g-butyrolactones (IIIh-j) substituted with
            electron-donating group on the phenyl ring.Keywords:
            b-phenyl-g-butyrolactones; b-propiolactone derivative; butenolides;
            2-phenyloxiranes; deamination; rearrangement
 CNR:
            5677393

 Author:
            Axiotis, Stella; Dreux, Jacques; Sollier, Jean-Claude; Chermat,
            Raymond; Poncelet, Martine; Simon, Pierre
 Reference:
            Journal, EJMCA5, Eur.J.Med.Chem.Chim.Ther., FR, 16, 5, 1981,
            431-438
 Title:
            TETRAHYDROPYRONES-2. I - SYNTHESES ET ACTIVITE
            PHARMACOLOGIQUE
 Abstract:
            The authors have shown that tetrahydropyran-2-ones and more
            particularly 3,4-diphenyl-6-methyl tetrahydropyran-2-one and
            4'-chloro-4-phenyl-6-methyl-3-phenyl tetrahydropyran-2-one have an
            interesting psychotropic activity.The synthesis of the different
            diastereoisomers of these two tetrahydropyran-2-ones have been
            described.A comparative study of the pharmacological properties of
            these diastereoisomers has shown that the activity observed is related
            to the stereochemistry of these compounds.
 CNR:
            5721360

 Author:
            Axiotis, Stella; Dreux, Jacques
 Reference:
            Journal, EJMCA5, Eur.J.Med.Chem.Chim.Ther., FR, 16, 5, 1981,
            439-445
 Title:
            TETRAHYDROPYRONES-2. II-DETERMINATION DES
            CONFIGURATIONS ET EXAMEN DE LA STEREOCHIMIE DES
            REACTIONS
 Abstract:
            The authors have determined the configuration and conformation of
            the diastereoisomers of 3,4-diphenyl-6-methyl tetrahydropyran-2-one
            and of 4'-chloro-4-phenyl-6-methyl-3-phenyl tetrahydropyran-2-one
            which synthesis and psychotropic properties have previously been
            described.It has not been possible to to determine directly the
            configuration of intermediates of linear structure but a correlation with
            tetrahydropyran-2-ones had been obtained.This correlation is
            particularly difficult to establish because of the epimerisation of the
            starting d-ketonitrils 1R*,2S* which is, in some cases, faster than their
            reaction.
 CNR:
            5721361

 Author:
            Ong, Helen H.; Profitt, James A.; Anderson, V. Brian; Kruse, Hansjoerg;
            Wilker, Jeffrey C.; Geyer, Harry M.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 24, 1, 1981, 74-79
 Title:
            Novel Tetracyclic Spiropiperidines. 1.
            3-Aryl-1,3-dihydrospiro<benzo<c>thiophene-1,4'-piperidines> as
            Potential Antidepressants
 Abstract:
            A series of
            3-aryl-1,3-dihydrospiro<benzo<c>thiophene-1,4'-piperidine>
            derivatives was synthesized and evaluated pharmacologically for
            potential psychotropic activity.Potent antidepressant-like activity was
            noted throughout the series, as assessed by tetrabenazine (TBZ)
            ptosis prevention in mice and potentiation of 5-hydroxytryptophan
            (5-HTP) induced behavioral effects in rats.A possible therapeutic
            advantage of the title compounds appears to be the overall low
            anticholinergic potential in comparison with the classic tricyclic
            antidepressants.Several congeners withnuclear halogen substitution
            also exhibited CNS stimulant properties, as evidenced by their ability
            to induce a dopamine agonist-like stereotypy and to increase the
            spontaneous motor activity in mice.
 CNR:
            5745579

 Author:
            Krogsgaard-Larsen, Povl; Brehm, Lotte; Schaumburg, Kjeld
 Reference:
            Journal, ACBOCV, Acta Chem.Scand.Ser.B, EN, 35, 5, 1981, 311-324
 Title:
            Muscimol, a Psychoactive Constituent of Amanita Muscaria, as a
            Medicinal Chemical Model Structure
 Abstract:
            The muschroom Amanita muscaria Fr., the fly agaric, has powerful
            psychotropic effects, which manifest themselves after consumption of
            the fresh or dried mushrooms.The use of the fly agaric as an inebriant
            among certain Siberian tribes may represent a degeneration of
            traditions, which played a decisive part in ancient Indo-European
            religious ceremonies.The plant Soma, which was deified and
            consumed by the Indo-European priests, probably is identical with
            Amanita muscaria Fr.
 CNR:
            5772561

 Author:
            Grimaldi, G.; Maggi, C. A.; Meli, A.
 Reference:
            Journal, JPPMAB, J.Pharm.Pharmacol., EN, 33, 1981, 194
 Title:
            Influence of some psychotropic agents on CaCl2-induced arrhythmias
            in the rat
 Abstract:
 CNR:
            5807586

 Author:
            Tobe, A.; Yoshida, Y.; Ikoma, H.; Tonomura, S.; Kikumoto, R.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 31, 8, 1981, 1278-1285
 Title:
            Pharmacological Evaluation of
            2-(4-Methylaminobutoxy)diphenylmethane Hydrochloride (MCI-2016),
            a New Psychotropic Drug with Antidepressant Activity
 Abstract:
            Pharmacological properties of
            2-(4-methylaminobutoxy)-diphenylmethane hydrochloride (MCI-2016)
            were examined in comparison with those of other
            antidepressants.MCI-2016 significantly antagonized the hypothermia
            and depression-like syndrome produced by reserpine
            injection.Furthermore, the drug exhibited such activities as
            anti-tetrabenazine and anti-cataleptic actions, and potentiation of the
            behavioral excitation induced by yohimbine, methamphetamine and
            L-dopa.MCI-2016 showed a definite suppressive effect on muricidal
            activity in olfactory bulb removed rats and the long-term
            isolation-induced fighting in mice without causing apparent motor
            disturbance.Judging from the effects of the drug on in vitro response to
            noradrenaline (NA) and serotonin (5-HT), and on
            p-chloramphetamine-induced hypermotility, it is suggested that
            MCI-2016 is a selective potentiator of NA presumably due to an
            inhibition of NA uptake.Anticholinergic and sedative actions of
            MCI-2016 were considerably weaker than those of amitriptyline and
            imipramine.Acute toxicity of MCI-2016 was the weakest among the
            drugs tested.These pharmacological profiles may suggest a potential
            clinical utility of MCI-2016 as a new psychotropic agent having an
            anti-depressant activity. - Key words: Antidepressants; MCI-2016;
            2-(4-Methylaminobutoxy)diphenylmethane hydrochloride,
            noradrenaline uptake, pharmacology; Psychotropic drugs
 CNR:
            5833960

 Author:
            Fontanella, L.; Corsico, N.; Diena, A.; Galliani, G.; Glaesser, A.
 Reference:
            Journal, FRPSAX, Farmaco Ed.Sci., EN, 36, 1, 1981, 3-12
 Title:
            SYNTHESIS OF NEW PSYCHOTROPIC 2-IMIDAZOLIDINONES
 Abstract:
            The report describes the synthesis and pharmacology of some new
            derivatives of 1-(m-or p-chlorophenyl)-2-imidazolidinone.These
            compounds were obtained either by reacting an amine with an
            N-(2-chloroethyl)-2-imidazolidinone or by reacting a
            2-chloroethylamine with an N-substituted-2-imidazolidinone.Two
            compounds (II f, h) showed interesting psychotropic activity.
 CNR:
            5862647

 Author:
            Vejdelek, Zdenek; Rajsner, Miroslav; Dlabac, Antonin; Ryska,
            Miroslav; Holubek, Jiri; et al.
 Reference:
            Journal, CCCCAK, Collect.Czech.Chem.Commun., EN, 45, 12, 1980,
            3593-3615
 Title:
            PSYCHOTROPIC DERIVATIVES OF
            5-PHENYL-7-CHLORO-1,3-DIHYDRO-1,4-BENZODIAZEPIN-2-ONE
            AND CONTRIBUTION TO THE SYNTHESIS OF ITS
            5-(2-CHLOROPHENYL) ANALOGUE
 Abstract:
            Alkylation of 7-chloro-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one (I)
            with 2,5-dimethoxyphenacyl bromide and 3-(4-phenylpiperazino)propyl
            chloride afforded the N-sunstituted derivatives of nordazepam III and
            IV; compound IV revealed properties of a potential hypnotic
            agent.Reaction of 4-chloronitrobenzene with (2-chlorphenyl)acetonitrile
            in methanolic solutions of alkali hydroxides gave mixtures from which
            following compounds were isolated:
            5-chloro-3-(2-chlorophenyl)2,1-benzisoxazole (VII), the O-methyloxime
            X, 5-chloro-2,3-bis(2-chlorophenyl)indole
            (XI),2-chloro-4'-nitrobenzophenone (XVII) and
            2-chloro-9-cyanoacridine N-oxide (XX).A similar reaction of
            4-chloronitrobenzene with (2-fluorophenyl)acetonitrile gave compound
            XX as the main product; in smaller amounts 4-nitroanisole,
            2-fluoro-4'-nitrobenzophenone (XVIII) and
            2-chloroacridine-9-carbonitrile (XXIV) were obtained.Compound VII
            was reduced to the aminobenzophenone derivative V which was
            transformed via the phtalimidoacetyl derivative VI to the
            chlorodemethyldiazepam II.
 CNR:
            5562410

 Author:
            Grinev, A. N.; Romanova, O. B.; Krichevskii, E. S.; Mashkovskii, M. D.;
            Andreeva, N. I.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 14, 8, 1980,
            527-532
 Title:
            SYNTHESIS AND PSYCHOTROPIC ACTIVITY OF NEW
            1,10-TRIMETHYLENE-1,2,3,4-TETRAHYDROPYRAZINO(1,2-a)INDOLE
            DERIVATIVES
 Abstract:
 CNR:
            5641448

 Author:
            Praliev, K. D.; Manatauov, D. M.; Belikova, N. A.; Sokolov, D. V.;
            Kurilenko, V. M.; et al.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 14, 9, 1980,
            620-622
 Title:
            SYNTHESIS OF DERIVATIVES OF PIPERIDINE AND
            DECAHYDROQUINOLINE, THEIR ANALGESIC AND
            PSYCHOTROPIC PROPERTIES. VII.
            1,2,5-TRIMETHYL-4-(N-PROPIONYLPHENYLAMINO)PIPERIDINE
 Abstract:
 CNR:
            5641858

 Author:
            Praliev, K. D.; Belikova, N. A.; Sokolov, D. V.; Kurilenko, V. M.; Khilenko, Zh.
            N.; Moiseeva, L. M.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 14, 12, 1980, 850-853
 Title:
            SYNTHESIS OF PIPERIDINE AND DECAHYDROQUINOLINE
            DERIVATIVES, THEIR ANALGESIC AND PSYCHOTROPIC PROPERTIES.
            IX.
            1-(4'-n-BUTOXYBUTYN-2'-YL)-4-PHENYL-4-PROPIONYLOXYPIPERIDINE
            AND ITS HYDROGENATION PRODUCTS
 Abstract:
 CNR:
            5642831

 Author:
            Nagai, Yasutaka; Hino, Katsuhiko; Uno, Hitoshi; Minami, Shinsaku
 Reference:
            Journal, CPBTAL, Chem.Pharm.Bull., EN, 28, 5, 1980, 1387-1393
 Title:
            Studies on Psychotropic Agents. VI. Synthesis of
            1'-Methylspiro<6-fluoroindan-1,3'-pyrrolidine>-3-one and Related
            Compounds
 Abstract:
            The title compounds (19) were synthesized by rearrangement of the
            1-ethoxycarbonyl-4-aryl-3,4-epoxypiperidines (7) to give the
            3-aryl-3-formylpyrrolidine derivatives (12) for pharmacological
            testing.Compound (19b) exhibited moderate central nervous system
            depressing activity.The mechanism of the rearrangement of
            1-substituted 4-aryl-3,4-epoxypiperidine with boron trifluoride etherate
            is discussed.Keywords -- spiro<indan-1,3'-pyrrolidine>-3-one;
            4-aryl-3,4-epoxypiperidine; rearrangement;
            4-amino-4'-fluorobutyrophenone; central nervous system depressing
            activity
 CNR:
            5665226

 Author:
            Mechoulam, R.; Lander, N.; Varkony, T. H.; Kimmel, I.; Becker, O.; et
            al.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 23, 10, 1980, 1068-1072
 Title:
            Stereochemical Requirements for Cannabinoid Activity
 Abstract:
            Several pairs of cannabinoid isomers were synthesized and tested for
            psychotropic activity in rhesus monkeys.Two regularities were
            observed: (a) In the absence of the other substituents, the equatorial
            stereochemistry of the substituent at C-1 determines activity. (b) Two
            groups of THC-type cannabinoids which differ only in that the chemical
            groupings in one of them at C-1, C-2 are situated at C-1, C-6 in the
            other (but retain their stereochemistry) have almost equivalent
            psychotropic activity.
 CNR:
            5701042

 Author:
            Praliev, K. D.; Esenalieva, M. Z.; Sokolov, D. V.; Kurilenko, V. M.;
            Khlienko, Zh. N.
 Reference:
            Journal, PCJOAU, Pharm.Chem.J.(Engl.Transl.), EN, 14, 10, 1980,
            699-702
 Title:
            SYNTHESIS OF DERIVATIVES OF PIPERIDINE AND
            DECAHYDROQUINOLINE AND THEIR ANALGESIC AND
            PSYCHOTROPIC PROPERTIES. VII. N-SUBSTITUTED
            2,3-DIMETHYL-4-PHENYL-4-HYDROXYPIPERIDINES AND THEIR
            PROPIONATES
 Abstract:
 CNR:
            5703226

 Author:
            Binder, Michael; Popp, Astrid
 Reference:
            Journal, HCACAV, Helv.Chim.Acta, EN, 63, 8, 1980, 2515-2518
 Title:
            Microbial Transformation of Cannabinoids. Part 3): Major Metabolites
            of (3R,4R)-D1-Tetrahydrocannabinol
 Abstract:
            The metabolic transformations of the psychotropic cannabinoid
            (3R,4R)-D1-tetrahydrocannabinol (5) (=D1-THC) by cultures of
            Fusarium nivale, Gibberella fujikuroi (both Ascomycetes) and
            Thamnidium elegans (Phycomycetes) were investigated.A number of
            metabolites, 1-4 and 6-9 were isolated from the incubations, partly
            purified and their structures elucidated by combined gas
            chromatography/mass spectrometry.Four of these metabolites,
            1"-hydroxy-D1-THC (4), 2"-hydroxy-D1-THC (1), 6b-hydroxy-D1-THC
            (8) and 2",6x-dihydroxy-D1-THC (9) so far have not been reported as
            microbial transformation products of 5.
 CNR:
            5778569

 Author:
            Netter, P.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., GE, 30, 8, 1980, 1179-1181
 Title:
            Drug Monitoring: Psychological Methods
 Abstract:
            Drug related mental and psychophysiological disturbances may be
            assessed by the same instruments of observation, ratings and
            self-ratings used for assessment of the efficacy of psychotropic
            drugs.Several possible sources of bias, however, concerning survey
            design, sample selection and evaluation and interpretation of data on
            adverse drug reactions have to be identified by careful documentation
            in order to exclude confounding factors, such as type and severity of
            treated and additional diseases, external events, personal factors in
            perception of symptoms by patient andphysician. - Key words: Drug
            monitoring, psychological methods
 CNR:
            5794156

 Author:
            Ott, H.; Fichte, K.; Hermann, W. M.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., GE, 30, 8, 1980, 1198
 Title:
            Classification of Psychotropic Drugs / The psychological performance
            profile
 Abstract:
 CNR:
            5794162

 Author:
            Zbinden, G.; Ettlin, R.; Bachmann, E.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 30, 10, 1980, 1709-1715
 Title:
            Electrocardiographic Changes in Rats during Chronic Treatment with
            Antidepressant and Neuroleptic Drugs
 Abstract:
            Five antidepressants, 3 phenothiazines and 5 butyrophenone
            neuroleptics were administered to rats orally at maximally tolerated
            doses for 22 weeks.The electrocardiogram (ECG) was recorded
            weekly.In animals treated with antidepressants quinidine-like changes
            of the atrioventricular and intraventricular conduction developed.There
            were also elevation of T-wave and right rotation of the electrical
            axis.Dibenzepine had the least effect on the ECG.In the group of
            phenothiazines, chlorpromazine induced tachycardia and thioridazine
            widening of the QRS complex.Prothipendyl had no
            effect.ECG-changes induced by some of the butyrophenone
            derivatives were tachycardia and widening of the QRS-complex.In rats
            treated with protriptyline the ECG changes were correlated with drug
            concentrations in serum and myocardial tissue.The studies provided a
            quantitative assessment of the cadiac effects of clinically proven
            psychotropic drugs.They will be useful as a baseline for the preclinical
            evaluation of new derivatives. - Key words: Antidepressants *
            Butyrophenones * Electrocardiogram, changes * Neuroleptics *
            Phenothiazines
 CNR:
            5796073

 Author:
            Ellis, K. O.; Wessels, F. L.; Burns, R. H.; Pong, S. F.
 Reference:
            Journal, JPMSAE, J.Pharm.Sci., EN, 69, 10, 1980, 1198-1202
 Title:
            Pharmacology of
            1-(3,4-dichlorobenzyl)-3,4,5,6-tetrahydro-2(1H)-pyrimidone, a Novel
            Antidepressant Compound with Antianxiety Activity
 Abstract:
            1-(3,4-dichlorobenzyl)-3,4,5,6-tetrahydro-2(1H)-pyrimidone (I) was
            evaluated in selected pharmacological tests, and its activity was
            compared to that of some clinically useful psychotropic drugs.Based
            on the results, it is evident that I has a unique profile of antidepressant
            and antianxiety activities that are evident in the same dose range.The
            mechanism of its antidepressant activity is proposed to be similar to
            the tricyclic antidepressants, that is, inhibition of norepinephrine
            uptake.Neither I nor the tricyclic antidepressants possess monoamine
            oxidaseinhibiting activity.However, unlike the tricyclic antidepressants,
            I is devoid of any significant anticholinergic activity and presumably is
            free of anticholinergic side effects.
 CNR:
            5799092

 Author:
            Wright, William B.; Greenblatt, Eugene N.; Day, Ivana P.; Quinones,
            Nicanor Q.; Hardy, Robert A.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 23, 4, 1980, 462-465
 Title:
            Derivatives of
            11-(1-Piperazinyl)-5H-pyrrolo<2,1-c><1,4>benzodiazepine as Central
            Nervous System Agents
 Abstract:
            Four 11-(1-piperazinyl)5H-pyrrolo<2,1-c><1,4>benzodiazepines were
            prepared and evaluated as central nervous system agents.All were
            active psychotropic agents as determined by animal screening
            tests.The most interesting compound,
            11-(1-piperazinyl)-5H-pyrrolo<2,1-c><1,4>benzodiazepine, showed
            dual activity as an antidepressant against tetrabenazine depression
            and as a neuroleptic as measured by protection vs. amphetamine
            lethality in grouped mice.
 CNR:
            5805235

 Author:
            Binder, Michael; Barlage, Uwe
 Reference:
            Journal, HCACAV, Helv.Chim.Acta, EN, 63, 1, 1980, 255-267
 Title:
            25. Metabolic Transformation of (3R,4R)-D1(7)-Tetrahydrocannabinol
            by a Rat Liver Microsomal Preparation
 Abstract:
            The metabolism of the non-psychotropic cannabinoid
            (3R,4R)-D1(7)-tetrahydro-cannabinol (1) (=D1(7)-THC) was investigated
            in a rat liver microsomal preparation.The metabolites obtained from
            the incubation mixture were separated, purified and identified by
            1H-NMR spectroscopy and combined gas-liquid
            chromatography/mass spectrometry.Metabolites 3-10 are derived from
            D1(7)-THC (1) by monohydroxylation in the isoprenoid moiety or the
            side chain of the molecule.Metabolites 11-16 are hydroxylated in the
            isoprenoid ring and the side chain simultaneously.The third group,
            metabolites 18-22, is derived from the 1,7-epoxide 17 by hydrolysis of
            the oxirane ring, three of these metabolites bearing additional
            hydroxyl-groups in the isoprenoid part or the side chain.The mass
            spectra of the metabolites are discussed in detail and a new rule for
            the fragmentations of tetrahydrocannabinols is presented.
 CNR:
            5859945

 Author:
            Riederer, P.; Lange, K. W.; Kornhuber, J.; Danielczyk, W.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 42, 22, 1992, 265-268
 Title:
            Glutamatergic-Dopaminergic Balance in the Brain Its importance in
            motor disorders and schizophrenia
 Abstract:
            Dopamine appears to be of less importance in the regulation of
            psychomotor functions than was previously thought.A central
            dopaminergic-glutamatergic balance may be important for both
            akinetic motor disorders and psychosis.In Parkinson's disease
            glutamate antagonists may counteract central glutamatergic
            hyperactivity and may be of value as anti-parkinsonian drugs.An
            increase of dopaminergic activity and/or a reduction of glutamatergic
            activity may contribute to the development of paranoid hallucinatory
            psychosis in schizophrenic patients and of pharmacotoxic psychosis in
            Parkinson's disease.Because of possibly severe side-effects of
            glutamatergic antagonists and agonists in the treatment of akinesia
            and psychosis, the development of partial glutamate
            agonists/antagonists could be an alternative strategy capable of
            producing antipsychotic or anti-kinetic effects with only mild adverse
            reaction. Key words: Brain, chemical information transmission,
            glutamatergic-dopaminergic
            balance.Dopamine.Glutamate.Parkinson's disease.Psychosis,
            pharmacotoxic.Schizophrenia
 CNR:
            5648251

 Author:
            Yevich, Joseph P.; New, James S.; Lobeck, Walter G.; Dextraze,
            Pierre; Brenstein, Edith; et al.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 35, 24, 1992, 4516-4525
 Title:
            Synthesis and Biological Characterization of
            a-(4-Fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazinebutanol and
            Analogues as Potential Atypical Antipsychotic Agents
 Abstract:
            A series of 1-(pyrimidin-2-yl)piperazine derivatives were prepared and
            evaluated in receptor binding assays and in in vivo behavioral
            paradigms as potential atypical antipsychotic agents.Compound 16
            (BMS 181100 (formerly BMY 14802)) emerged as the lead compound
            from within the series on the basis of its good activity and duration of
            action in the inhibition of both conditioned avoidance responding and
            apomorphine-induced stereotopy in the rat.Compound 16 not only
            failed to induce catalepsy in the rat but was quite effective in reversing
            the cataleptic effect of neurolepti c agents, thus indicating a low
            propensity for causing extrapyramidal side effects.In comparison to
            reference antipsychotic agents, 16 appeared to be less sedating and
            was relatively weaker in causing muscle incoordination.The
            compound was essentially inactive in binding to dopamine D2
            receptors and its chronic administration to rats did not result in
            dopamine receptor supersensitivity.It exhibited modest to weak affinity
            for 5-HT1A and a1 receptors but was found to be a fairly potent ligand
            for s binding sites (IC50 vs (+)-<3H>-3-PPP = 112 nM).Although the
            resolved enantiomers of racemic 16 did not show dramatic differences
            from racemate or from each other in most tests, the R(+) enantiomer
            was up to 11-fold more potent than its antipode in binding to s
            sites.Several studies have indicated that 16 may be a limbic-selective
            agent which may modulate dopaminergic activity by an indirect
            mechanism.The compound has been selected for clinical evaluation in
            the treatment of psychosis.
 CNR:
            5712273

 Author:
            Russell, Michael G. N.; Baker, Raymond; Billington, David C.; Knight,
            Antony K.; Middlemiss, Derek N.; Noble, Alison J.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 35, 11, 1992, 2025-2033
 Title:
            Benz<f>isoquinoline Analogues as High-Affinity s Ligands
 Abstract:
            This paper describes the synthesis of some conformationally restricted
            4-phenylpiperidine analogues and their affinities for the guinea pig
            cerebellum s recognition site (<3H>-DTG) and the rat striatum
            dopamine D2 receptor (<3H>-(-)-sulpiride) in order to develop potent
            selective s ligands as tools in the investigation of this site in
            psychosis.It was found that both hexa- and octahydrobenz<f>
            isoquinolines with lipophilic N-substituents had high affinities for the s
            site.Notably,
            trans-3-cyclohexyl-1,2,3,4,4a,5,6,10b-octahydrobenz<f>isoquinoline
            (26) had anaffinity of 0.25 nM making it the highest affinity s ligand
            reported to date.Moreover, it is at least 10000-fold selective over the D2
            receptor and could prove to be a valuable tool in the study of s
            sites.Other analogues such as 1H-indeno<2,1-c>pyridines and
            1H-benzo<3,4>cyclohepta<1,2-c>pyridines also displayed high s site
            affinity.
 CNR:
            5854565

 Author:
            Bjoerkman, Sven; Elisson, Lars Ove; Gabrielsson, Johan
 Reference:
            Journal, JPPMAB, J.Pharm.Pharmacol., EN, 41, 1989, 160-163
 Title:
            Pharmacokinetics of Quinacrine after Intrapleural Instillation in Rabbits
            and Man
 Abstract:
            Quinacrine was given by intrapleural instillation or intravenous infusion
            to 10 rabbits.The uptake of quinacrine from the pleural space was
            rapid and complete.The mean absorption half-life was approximately 7
            min and the mean bioavailability was slightly in excess of
            100percent.Similar absorption characteristics generally applied in
            man, in a pilot study in four patients.In three of them, peak quinacrine
            plasma concentrations were reached that were far above the normal
            therapeutic range.Known systemic side-effects of of quinacrine
            comprise CNS stimulation, toxic psychosis and convulsions.In view of
            the high bioavailability and the large doses used for pleural sclerosing
            (pleurodesis) in patients, neurological disease and psychiatric
            disturbances that prediscope to CNS toxicity should be considered as
            contraindications to intrapleural quinacrine.
 CNR:
            5879255

 Author:
            New, James S.; Yevich, Joseph P.; Temple, Davis L.; New, Kimberly
            B.; Gross, Sharon M.; et al.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 31, 3, 1988, 618-624
 Title:
            Atypical Antipsychotic Agents: Patterns of Activity in a Series of
            3-Substituted 2-Pyridinyl-1-piperazine Derivatives
 Abstract:
            A series of 3-substituted 2-pyridinyl-1-piperazine derivaties have been
            appended to cyclic imide groups and evaluated for their potential
            antipsochotic activity.The dopamine receptor affinities of these target
            molecules, as well as their ability to block apomorphine-induced
            stereotypy or reverse neuroleptic-induced catalepsy, was dependent
            on the lipophilic and electronic characteristics of the substituent
            situated on the pyridine ring.Groups with +s and -p values were most
            consistent with the desired biological profile of the target molecules,
            the cyano moiety being the optimum choice.Evaluation of compound
            12 in a monkey model of amphetamine psychosis, and the regional
            selectivity it expresses for the A10 dopaminergic cell bodies in
            electrophysiological experiments, suggest this compound would be an
            atypical antipsychotic agent with few side effects.
 CNR:
            5837720

 Author:
            Christensen, I.; Geismar, L.; Kirkegaard, Aa.; Kirkegaard, G.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 36, 5, 1986, 855-860
 Title:
            Additional Studies on Side Effects of Melperone in Long-term Therapy
            for 1 - 20 Years in Psychiatric Patients
 Abstract:
            The present study reporting on continuous melperone treatment of
            hitherto longest duration recorded in literature was conducted in order
            to reveal side effects of long-term melperone therapy. 50 patients, 24
            females and 26 males, aged 37 - 102 (average: 81 years of age) were
            treated with melperone (Buronil, Bunil, Eunerpan) for 1 to 20 years.In
            most patients, daily dosage varied from 10 to 300 mg, total dosage
            ranging from 6510 mg to 1 662 225 mg, avr. 203 923 mg.Diagnoses
            were as follows: senile dementia (14), organic dementia (9),
            arterio-sclerotic dementia (8), schizophrenia (17) and nonspecific
            psychosis (2).The patients were examined for clinical side effects
            including abnormal ECGs and ophthalmological
            diseases.Biochemical laboratory tests comprised sedimentation rate,
            haemoglobin, leucocytes, creatinine, alanine-aminotransferase,
            g-glutamyl-transferase and bilirubin.The results were evaluated by a
            specialist in internal medicine and an ophthalmologist performed the
            examinations on the 20 patients who were able to cooperate.The
            conclusion was that no serious side effects were observed which could
            with any certainty be related to melperone therapy. - Key words:
            Antipsychotic drugs; Bunil; Buronil; Butyrophenone; Eunerpan;
            Melperone, clinical studies, long-term treatment, side effects
 CNR:
            5795096

 Author:
            Metzger. Erich; Ammann, Daniel; Asper, Robert; Simon, Wilhelm
 Reference:
            Journal, ANCHAM, Anal.Chem., EN, 58, 1, 1986, 132-135
 Title:
            Ion Selective Liquid Membrane Electrode for the Assay of Lithium in
            Blood Serum
 Abstract:
            The lipophilic neutral carrier
            N,N-dicyclohexyl-N',N'-diisobutyl-cis-cyclohexane-1,2-dicarboxamide
            has been tested in different liquid membranes in order to evaluate its
            potential use in the potentiometric assay of Li+ in blood serum for
            monitoring the lithium therapy of manic-depressive psychosis.One of
            the membranes showed sufficient selectivity against the interfering
            cations for the Li+ assay in blood using a fixed potential,
            reproducibility, and the response time in aqueous solutions and serum
            make a practical use of Li+-selective electrodes based on this
            membrane possible.
 CNR:
            5871045

 Author:
            Agarwal, D. P.; Hoo, J. J.; Tjaden, A.; Nishigaki, I.; Beckermann, W. J.;
            et al.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 35, 11, 1985, 1639-1642
 Title:
            Effect of Amphetamine on Brain Catecholamines, Brain b-Endorphin,
            Serum Prolactin, Catechol-O-methyltransferase and Monoamine
            Oxidase of Various Organs in the Rat
 Abstract:
            Rats were treated with amphetamine to induce an amphetamine
            psychosis which resembles paranoid schizophrenia.Brain
            catecholamines, brain b-endophrin, serum prolactin as well as
            catechol-O-methyltransferase and monoamine oxidase were
            subsequently measured.The norepinephrine levels were significantly
            lower in brain regions of rats treated with amphetamine whereas levels
            of dopamine and b-endorphin remained the same.No significant
            changes were found in the levels of catechol-O-methyltransferase,
            monoamine oxidase and serum prolactin.In view of recent findings by
            other investigators in this field, our results suggest an important role of
            the adrenergic system in the pathogenesis of amphetamine psychosis.
            - Key words: Amphetamine, pharmacology; b-Endorphin;
            Catecholamines; Catechol-O-methyltransferase; Monoamine oxidase;
            Prolactin
 CNR:
            5833843

 Author:
            Kirkegaard, A.; Hammershoj, E.; Ostergard, P.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 32, 4, 1982, 465-468
 Title:
            Evaluation of Side Effects due to Cloazepine in Long-term Treatment
            of Psychosis
 Abstract:
            17 patients (13 males and 4 females) were examined for side effects
            due to long-term treatment with
            8-chloro-11-(4-methylpiperazin-1-yl)-5H-dibenzo(b,e)(1,4)diazepine
            (clozapine) with emphasis on alterations in bone marrow, liver, and
            kidney function. 16 patients were schizophrenic, one patient was
            diagnosed psychosis e causa dubia.The age range was 25-68 years,
            with an average of 38.2 years.The daily clozapine dose varied from
            225 to 800 mg with a total intake during the trial period of 149.1-891.6
            g yielding an average of 479.8 g.The treatment period varied from 20
            to 51 months, with an average of 35.9 months.None of the patients had
            to discontinue the treatment because of side effects.The laboratory
            data including hematological, and nephrological parameters revealed
            no significant changes related to clozapine treatment within the
            treatment period.No changes were observed in ECG. 12 patients
            experienced side effects, 8 of them receiving concomitant psycholeptic
            medication. 9 patients complained of temporary fatigue and 5 of these
            experienced continuous drowsiness.There were 8 cases of nocturnal
            hypersalivation and two cases of increased appetite.One patient
            developed light tachycardia and one patient orthostatic
            hypotension.Clozapine is known to be an effective anti-psychotic drug,
            but due to reports of agranulocytosis in 16 Finnish patients the drug
            was withdrawn from the Danish market in 1975 although later its use
            was merely restricted to special cases. This study does not indicate
            that clozapine contains greater risk of clinical side effects than
            commonly used psycholeptic drugs. - Key words: Clozapine, long-term
            treatment, side effects .Psycholeptics
 CNR:
            5734258

 Author:
            Iwanami, Sumio; Takashima, Mutsuo; Hirata, Yasufumi; Hasegawa, Osamu; Usuda,
            Shinji
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 24, 10, 1981, 1224-1230
 Title:
            Synthesis and Neuroleptic Activity of Benzamides.
            cis-N-(1-Benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino)benzamide
            and Related Compounds
 Abstract:
            Three series of benzamides of N,N-disubstituted ethylenediamines (linear
            alkane-1,2-diamines), 1-substituted 2-(aminomethyl)pyrrolidines, and 1-substituted
            3-aminopyrrolidines (cyclic alkane-1,2-diamines) were designed and synthesized as
            potential neuroleptics.All target compounds were evaluated for their inhibitory effects on
            apomorphine-induced stereotyped behavior in rats, and a good correlation between
            structure and activity was found throughout the series.In the linear series (analogues of
            metoclopramide), introduction of a benzyl group on the terminal nitrogen, rather than an
            ethyl group, and a methyl group on the p-amino group of metoclopramide both enhanced
            the activity.The resulting
            N-<2-(N-benzyl-N-methylamino)ethyl>-5-chloro-2-methoxy-4-(methylamino)benzamide
            (23) was about 15 times more active than metoclopramide.In the cyclic series,
            particularly among the benzamides of 1-benzyl-3-aminopyrrolidine, most of the
            compounds tested were more active than the corresponding linear benzamides.
            cis-N-(1-Benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino)benzamide
            (YM-09151-2, 55) was the most active among all of the compounds tested, being 13 and
            408 times more potent than haloperidol and metoclopramide, respectively.Moreover,
            compound 55 exhibited a fairly high ratio of antistereotypic activity to cataleptogenicity
            compared with haloperidol and metoclopramide.It is expected that compound 55 may be
            used as a potent drug with few side effects in the treatment of psychosis.
 CNR:
            5698222


 Author:
            Eroglu, L.; Atamer-Simsek, S.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 30, 12, 1980, 2115-2117
 Title:
            Effect of Lithium on Stress-induced Changes in the Brain Levels of
            Monoamines in Rats
 Abstract:
            The effect of lithium on the brain levels of monoamines was examined
            in stress-exposed rats.It was found that stress lowered brain levels of
            noradrenaline and serotonin and had no effect on the brain level of
            dopamine.Lithium, alone , caused a decrease in brain levels of
            noradrenoline and dopamine, but not in serotonin.Nevertheless, the
            diminished level of serotonin in stress-exposed rats increased by
            lithium treatment.It may be possible to make a correlation between the
            latter finding with the inhibitory effect of lithium on aggression in
            human beings and animals. - Key words: Lithium * Monoamines *
            Psychosis, manic-depressive * Stress
 CNR:
            5795951
