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hallucinogen
hallucinogenic

 Author:
          Gomez-Jeria, Juan Sebastian; Cassels, Bruce K.; Saavedra-Aguilar,
          Juan Carlos
 Reference:
          Journal, EJMCA5, Eur.J.Med.Chem.Chim.Ther., EN, 22, 1987,
          433-438
 Title:
          A QUANTUM-CHEMICAL AND EXPERIMENTAL STUDY OF
          THE HALLUCINOGEN
          (+/-)-1-(2,5-DIMETHOXY-4-NITROPHENYL)-2-AMINOPROPANE
          (DON)
 Abstract:
          The electronic structure of
          1-(2,5-dimethoxy-4-nitrophenyl)-2-aminopropane (DON) was
          calculated at the CNDO/2 level, and the racemic compound was
          synthesized and found to be hallucinogenic at doses of 4 mg.DON
          differs from its similarly active congeners in that a hydrophilic nitro
          group replaces lipophilic substituents at C-4 of the benzene ring.The
          implications for the mechanism of serotonin receptor binding of these
          drugs are discussed.Keyords: frontier molecular orbitals / CNDO/2/
          electrophilic superdelocalizability / atomic charge / lipophilicity /
          serotonin receptor affinity / hallucinogenic potency / DON
 CNR:
          5676912


 Author:
          Nichols, David E.; Hoffman, Andrew J.; Oberlender, Robert A.;
          Riggs, Robert M.
 Reference:
          Journal, JMCMAR, J.Med.Chem., EN, 29, 2, 1986, 302-304
 Title:
          Synthesis and Evaluation of 2,3-Dihydrobenzofuran Analogues
          of the Hallucinogen
          1-(2,5-Dimethoxy-4-methylphenyl)-2-aminopropane: Drug
          Discrimination Studies in Rats
 Abstract:
          Two analogues,
          6-(2-aminopropyl)-5-methoxy-2,3-dihydrobenzofuran and
          6-(2-aminopropyl)-5-methoxy-2-methyl-2,3-dihydrobenzofuran,
          of the hallucinogenic agent
          1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM)
          were synthesized and tested in the two-lever drug
          discrimination paradigm.In rats trained to discriminate saline
          from LSD tartrate (0.08 mg/kg), stimulus generalization
          occurred to both of the 2,3-dihydrobenzofuran analogues but at
          doses more than 10-fold higher than for DOM.A possible
          explanation for this dramatic attenuation of LSD-like activity
          could involve a highly directional electrophilic binding site on
          the receptor that cannot accept the orientation of the unshared
          electron pairs on the heterocyclic oxygen atom in the
          benzofurans.
 CNR:
          5745610


 Author:
          Nozoe, Shigeo; Koike, Yutaka; Ito, Noriie; Kusano,
          Genjiro
 Reference:
          Journal, CMLTAG, Chem.Lett., EN, 1984, 1001-1002
 Title:
          ISOLATION AND STUCTURE OF
          GYMNOPRENOL-D, A HOMOLOGOUS SERIES
          OF FULLY HYDRATED
          POLYISOPRENEPOLYOL FROM GYMNOPYLUS
          SPECTABILIS
 Abstract:
          Gymnoprenol-D, a homologous series of fully
          hydrated polyisoprenepolyol having a glycerol
          terminus has been isolated from an hallucinogen
          mushroom, Gymnopilus spectabilis along with an
          analogous compound with one double bond.The
          structure of these polyols was determined by a
          combination of chemical degradation and
          spectroscopic analyses.
 CNR:
          5667658


 Author:
          Oberlender, Robert A.; Kothari, Paresh J.; Nichols, David E.;
          Zabik, Joseph E.
 Reference:
          Journal, JMCMAR, J.Med.Chem., EN, 27, 6, 1984, 788-792
 Title:
          Substituent Branching in Phenethylamine-Type Hallucinogens:
          A Comparison of
          1-<2,5-Dimethoxy-4-(2-butyl)phenyl>-2-aminopropane and
          1-<2,5-Dimethoxy-4-(2-methylpropyl)phenyl>-2-aminopropane
 Abstract:
          Two novel hallucinogen analogues related to
          1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM,
          STP) were synthesized and evaluated in the two-lever drug
          discrimination paradigm by using 0.08 mg/kg of LSD at the
          training drug stimulus.The two compounds differ from each
          other with respect to the point of branching in the 4-alkyl
          group.However, pharmacological evaluation revealed a clear
          difference in potency and degree of LSD generalization for the
          two isomers.Branching adjacent to the ring, as in the 4-(2-butyl)
          analogue, may provide steric interference to the formation of the
          drug-receptor complex, while branching one methylene unit
          removed from the ring, as in the 4-(2-methylpropyl) analogue,
          poses less of a steric problem for the drug-receptor
          interaction.This is consistent with the idea that formation of a
          charge-transfer complex between the hallucinogen molecule
          and the receptor may be one of the features of this
          drug-receptor interaction.
 CNR:
          5699046

 Author:
          Glennon, Richard A.; Jacyno, John M.; Young, R.;
          McKenney, J. D.; Nelson, David
 Reference:
          Journal, JMCMAR, J.Med.Chem., EN, 27, 1, 1984,
          41-45
 Title:
          Synthesis and Evaluation of a Novel Series of
          N,N-Dimethylisotryptamines
 Abstract:
          A novel series of N,N-dimethylisotryptamine
          (isoDMT) derivatives, i.e., derivatives of
          1-<2-(dimethylamino)ethyl>indole, was prepared and
          found to be isosteric with their corresponding
          N,N-dimethyltryptamine (DMT) counterparts with
          respect to serotonin receptor (rat fundus)
          affinity.Whereas the isoDMT derivatives possessed a
          greater affinity than did their corresponding DMT
          derivatives, They were relatively ineffective in
          displacing <3H>-5-HT binding from rat brain (cortex)
          homogenates.In a drug discrimination paradigm, using
          rats as subjects, 6-OMe-isoDMT produced eff ects
          similar to those of 5-OMe-DMT.Attempts to
          antagonize the discriminative stimulus effects of the
          hallucinogen
          1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane
          (DOM) using two of isoDMT derivatives proved
          unsuccessful.
 CNR:
          5700956

 Author:
          Jacob, James N.; Nichols, David E.
 Reference:
          Journal, JMCMAR, J.Med.Chem., EN, 25, 5, 1982,
          526-530
 Title:
          Isomeric Cyclopropyl Ring-Methylated Homologues of
          trans-2-(2,5-Dimethoxy-4-methylphenyl)cyclopropylamine,
          an Hallucinogen Analogue
 Abstract:
          The hallucinogen analogue
          trans-2-(2,5-dimethoxy-4-methylphenyl)cyclopropylamine
          was modified by adding a 3-methyl group, either cis or trans
          with respect to the amino group.These two isomeric
          cyclopropyl ring-methylated compounds were then tested
          for activity in the mouse ear-scratch assay and for a
          contractile effect in the rat fundus preparation.Neither
          compound was found to possess appreciable activity when
          compared to the nonmethylated parent, in either assay.
 CNR:
          5639867


 Author:
          Glennon, Richard A.; Young, Richard; Benington,
          Fredrick; Morin, Richard D.
 Reference:
          Journal, JMCMAR, J.Med.Chem., EN, 25, 10, 1982,
          1163-1168
 Title:
          Behavioral and Serotonin Receptor Properties of
          4-Substituted Derivatives of the Hallucinogen
          1-(2,5-Dimethoxyphenyl)-2-aminopropane
 Abstract:
          The serotonin (5-HT) receptor affinities and behavioral
          (discriminative stimulus) properties of a series of
          4-substituted derivatives of
          1-(2,5-dimethoxyphenyl)-2-aminopropanes (2,5-DMA)
          were investigated.The substituents at the 4-position
          included H, OMe, OEt, Me, Et, F, Br, I, and
          NO2.Substituent lipophilicities (p values) of these
          functionalities appear to have a minimal effect on either
          5-HT receptor affinity or behavioral activity.Those
          derivatives previously found to be most potent in human
          studies possess significant affinity for 5-HT
          receptors.Furthermore, when rats trained to discriminate
          (+/-)-1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropame
          (DOM) from saline were used, generalization was found
          to occur upon administration of the 4-substituted 2,5-DMA
          derivatives.Because a direct relationship exists between
          the ED50 values obtained from these discrimination
          studies and human hallucinogenic potencies, the
          discriminative stimulus paradigm, with DOM as a training
          drug, appears to be a useful tool for comparing the
          quantitative and qualitative (DOM-like) effects produced
          by certain hallucinogenic agents.
 CNR:
          5805713

 Author:
          McQuinn, Roy L.; Cone, Edward J.; Shannon, Harlan
          E.; Su, Tsung-Ping
 Reference:
          Journal, JMCMAR, J.Med.Chem., EN, 24, 12, 1981,
          1429-1432
 Title:
          Structure-Activity Relationships of the Cycloalkyl Ring
          of Phencyclidine
 Abstract:
          In order to investigate the structural requirements for a
          cycloalkyl moiety in the potent hallucinogen
          1-(1-phenylcyclohexyl)piperidine (PCP, 1), a series of
          structural analogues was synthesized in which the size
          of the cycloalkyl ring was varied from three carbons to
          eight carbons.Biological activities of these compounds
          were assessed in an in vitro assay (phencyclidine
          binding assay) and an in vivo assay (discriminative
          stimulus assay).As the cycloalkyl ring size decreased
          from that of cyclohexane (PCP), PCP-like activity
          declined in both assays, but as the cycloalkyl ring size
          became larger than cyclohexane, a sharp decline in
          PCP-like activity was observed in the in vivo assay,
          while activity in the in vitro assay was only slightly
          less than that of PCP. 1-(1-Phenylcyclooctyl)piperidine
          (8) had potent competitive binding properties in the in
          vitro binding assay but produced no observable
          PCP-like effects in the in vivo assay.The importance
          of the cycloalkyl ring in the structure of PCP was
          demonstrated by testing benzylpiperidine (2), which
          had almost no measurable activity in either assay.
 CNR:
          5638087


 Author:
          Weintraub, Herschel J.; Nichols, David E.; Makriyannis,
          Alexandros; Fesik, Stephen W.
 Reference:
          Journal, JMCMAR, J.Med.Chem., EN, 23, 3, 1980, 339-341
 Title:
          Conformational Energy Differences between Side Chain
          Alkylated Analogues of the Hallucinogen
          1-(2,5-Dimethoxy-4-methylphenyl)-2-aminopropane
 Abstract:
          Theoretical conformational energy calculation were carried out for
          the (+) and (-) isomers of the hallucinogen
          1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM,
          STP).Energies were also calculated for two analogues of DOM
          1-amino-1-(2,5-dimethoxy-4-methylbenzyl)cyclopropane and
          1-(2,5-dimethoxy-4-methylphenyl)-2-methyl-2-aminopropane.The
          method utilized classical, empirical potential-energy functions.A
          previously proposed active conformational region was
          studied.Compounds could be ranked in order of potency based on
          relative conformational energies in this region.Measurement of
          13C spin-lattice relaxation times (T1) for the two a,a-disubstituted
          DOM analogues confirmed theoretical predictions of very
          restricted conformational freedom for the dimethyl compound but
          more flexibility for the cyclopropane analogue.
 CNR:
          5697440


 Author:
          Glennon, R. A.; Schubert, E.; Jacyno, J. M.;
          Rosecrans, J. A.
 Reference:
          Journal, JMCMAR, J.Med.Chem., EN, 23, 11, 1980,
          1222-1226
 Title:
          Studies on Several 7-Substituted
          N,N-Dimethyltryptamines
 Abstract:
          Several 7-substituted derivatives of
          N,N-dimethyltryptamine (DMT) were prepared and
          evaluated in the rat fundus serotonin receptor assay
          and in a behavioral (discriminative stimulus) assay in
          rats.Both 7-Me- and 5-Ome-7-Me-DMT possess a
          higher pA2, and 5,7-(OMe)2-DMT a lower pA2, than
          that of DMT itself.Like DMT, all three of these
          compounds produce behavioral effects in rats which
          are similar to those of the hallucinogen
          5-OMe-DMT.Although 7-Et- and 7-Br-DMT possess
          a higher serotonin receptor affinity than DMT, neither
          produce behavioral effects which parallelthose of
          5-OMe-DMT.In contrast, 6-OMe-DMT and its
          5-OMe derivative do not interact with the serotonin
          receptors in a competitive manner and are inactive in
          the discriminative stimulus assay.
 CNR:
          5698464


 Author:
            Oberlender, Robert; Ramachandran, P. V.; Johnson, Michael P.;
            Huang, Xuemei; Nichols, David E.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 38, 18, 1995, 3593-3601
 Title:
            Effect of a Chiral 4-Alkyl Substituent in Hallucinogenic
            Amphetamines
 Abstract:
            The potency of hallucinogenic amphetamine derivatives of the
            1-(2,5-dimethoxy-4-alkylphenyl)-2-aminopropane type drops
            dramatically when the length of the 4-alkyl substituent exceeds
            propyl or when the substituent is branched.This investigation was
            directed toward evaluating changes in behavioral and
            biochemical pharmacology resulting from introducing chirality
            into the 4-alkyl group of such analogues.Two diastereomeric
            derivatives of this class containing a 4-(R or S)-2-butyl
            substituent, 11a,b, respectively, were studied.A slight but
            nonsignificant potency difference in d-lysergic acid diethylamide
            tartrate (LSD)-like discriminative stimulus properties and equal
            affinity for
            <125I>-(R)-(2,5-dimethoxy-4-iodophenyl)isopropylamine-labeled
            serotonin 5-HT2A/C radioligand-binding sites were
            observed.Thus, the portion of the receptor that interacts with the
            4-alkyl substituent on hallucinogenic amphetamines does not
            present a highly asymmetric environment to the ligand.However,
            since both test drugs had higher binding affinity but lower
            LSD-like behavioral potency than the prototype compound with
            a 4-methyl group
            (2,5-dimethoxy-4-methylphenyl)isopropylamine, 2), 11a,b may
            differ in their receptor agonist efficacy from more behaviorally
            active compounds such as 2.
 CNR:
            6001414

 Author:
            Jara, Aida Neira; Torres, Milton Aillon; Cassels, Bruce
            Kennedy; Rezende, Marcos Caroli
 Reference:
            Journal, SYNCAV, Synth.Commun., EN, 24, 3, 1994, 417-426
 Title:
            Some Fluoro and Nitro Analogues of Hallucinogenic
            Amphetamines
 Abstract:
            The preparation of the fluoro and nitro analogues (2)-(5) of the
            hallucinogens 2,4,5-trimethoxy- and
            2-methoxy-4,5-methylenedioxy-amphetamine is described.
 CNR:
            5896233


 Author:
            Nichols, David E.; Frescas, Stewart; Marona-Lewicka, Danuta;
            Huang, Xuemei; Roth, Bryan L.; et al.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 37, 25, 1994,
            4346-4351
 Title:
            1-(2.5-Dimethoxy-4-(trifluoromethyl)phenyl)-2-aminopropane:
            A Potent Serotonin 5-HT2A/2C Agonist
 Abstract:
            A method was found to synthesize
            1-(2,5-dimethoxy-4-(trifluoromethyl)phenyl)-2-aminopropane,
            5, and its des-a-methyl congener
            2-(2,5-dimethoxy-4-(trifluoromethyl)phenyl)aminoethane, 6,
            the trifluoromethyl analogs of substituted hallucinogenic
            phenethylamine derivatives such as
            1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (3, DOI) that
            are potent 5-HT2A/2C agonists.In our hands, 5 and 6 have
            proven to have affinity for <3H>ketanserin or <125I>-3-labeled
            5-HT2A/2C sites in rat cortex comparable to or higher than the
            analogous bromo or iodo analogs.Similarly,5 and 6 had potency
            comparable to or slightly greater than that of their bromo or iodo
            congeners in the two-lever drug discrimination assay in rats
            trained to discriminate saline from LSD tartrate.The agonist
            properties of 5 and 6 were evaluated by measuring the
            accumulation of <3H>inositol monophosphate in cultured cells
            selectively expressing either 5-HT2A or 5-HT2C receptors.In
            comparison to serotonin (5-HT), compound 3 (DOI), 5, and 6
            were eqally efficacious and full agonists at the 5-HT2C
            receptor.Similarly, 3 and 5 produced equivalent responses at
            the 5-HT2A receptor as compared to 5-HT.In contrast, 6, the
            a-desmethyl analog of 5, was only half as potent at stimulating
            inositol monophosphate accumulation at the 5-HT2A receptor.In
            conclusion, the title compound 5 and its a-desmethyl congener
            6 appear to be the most potent of the so-called hallucinogenic
            amphetamine 5-HT agonists reported to date.Further, the
            reduced efficacy of 6 at the 5-HT2A receptor may offer at least
            a partial explanation for the observed higher in vivo potencies
            of a-methyl-substituted compounds in this series.
 CNR:
            5946149

 Author:
            Tanaka, Masayasu; Hashimoto, Kimiko; Okuno, Toshikatsu;
            Shirahama, Haruhisa
 Reference:
            Journal, PYTCAS, Phytochemistry, EN, 34, 3, 1993, 661-664
 Title:
            NEUROTOXIC OLIGOISOPRENOIDS OF THE
            HALLUCINOGENIC MUSHROOM, GYMNOPILUS
            SPECTABILIS
 Abstract:
            New gymnopilins (with m = 3, n = 5 and 6) were isolated from
            Gymnopilus spectabilis and their structures were deduced from
            spectral data and degradation studies.Depolarizing activity was
            found for the gymnopilins with m = 2 and 3 and the activity of
            the compounds with m = 2 increased in the following order: n =
            7 < n = 6 < n = 5.
 CNR:
            5845204

 Author:
            Oberlender, Robert; Pfaff, Robert C.; Johnson, Michael P.;
            Huang, Xuemei; Nichols, David E.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 35, 2, 1992, 203-211
 Title:
            Stereoselective LSD-like Activity in d-Lysergic Acid Amides
            of (R)- and (S)-2-Aminobutane
 Abstract:
            The (R)- and (S)-2-butylamides of d-lysergic acid were
            prepared and evaluated in behavioral and biochemical assays of
            5-HT2 agonist activity.In rats trained to discriminate 0.08 mg/kg
            LSD tartrate from saline, both isomers completely substituted
            for the training stimulus.Similarly, both isomers were found to
            possess very high affinity in displacing <125I>-(R)-DOI
            (<125I>-(R)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane)
            from rat cortical homogenate 5-HT2 receptors and in displacing
            <3H>-8-OH-DPAT
            (<3H>-8-hydroxy-2-(di-n-propylamino)tetralin) from rat
            hippocampal5-HT1A receptors.The difference in activity
            between the two isomeric amides was significant in both
            behavioral and binding assays, with the R isomer possessing
            greater potency.Molecular mechanics were used to predict the
            active geometries of the subject compounds.It was found that
            the (R)-2-butylamide has a conformation quite similar to LSD,
            while the (S)-2-butylamide does not.These results suggest that
            stereochemical properties of the amide substituent of
            hallucinogenic lysergamides may exert a critical influence on
            activity.It is concluded that the conformation of the amide
            function may directly affect binding through stereoselective
            interactions with a hydrophobic region on the receptor,
            indirectly by inducing conformational changes elsewhere in the
            molecule, or by a combination of these two mechanisms.
 CNR:
            5596717

 Author:
            Tomaszewski, Zbigniew; Johnson, Michael P.; Huang,
            Xuemei; Nichols, David E.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 35, 11, 1992,
            2061-2064
 Title:
            Benzofuran Bioisosteres of Hallucinogenic Tryptamines
 Abstract:
            The benzofuran analogues of the hallucinogens
            5-methoxy-N,N-dimethyltryptamine and
            5-methoxy-a-methyltryptamine were synthesized and evaluated
            for affinity at the serotonin 5-HT2 and 5-HT1A receptors in rat
            brain homogenate, labeled with
            <125I>-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
            (<125I>DOI) and
            <3H>-8-hydroxy-2-(N,N-di-n-propylamino)tetralin
            (<3H>-8-OH-DPAT), respectively.At the 5-HT2 receptor, the
            benzofurans had slightly decreased affinities, approximately
            one-third and one-sixth those of the indoles, for the primary
            amines and the tertiary amines, respectively.The benzofurans
            also had lower affinity at the 5-HT1A receptor, but decreased
            only about 20-30percent from that of the indole isosteres.Thus,
            the 5-HT1A receptor is less discriminating with respect to
            preference for an indole versus a benzofuran, although all of
            the compounds did have higher affinities for the 5-HT2 receptor
            than for the 5-HT1A receptor.It is suggested that benzofurans
            may be useful in the design of serotonin receptor ligands.
 CNR:
            5856229

 Author:
            Nichols, Dawid E.; Snyder, Scott E.; Oberlender, Robert;
            Johnson, Michael P.; Huang, Xuemei
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 34, 1, 1991, 276-281
 Title:
            2,3-Dihydrobenzofuran Analogues of Hallucinogenic
            Phenethylamines
 Abstract:
            Two 2,3-dihydrobenzofuran analogues of hallucinogenic
            amphetamines were prepared and evaluated for activity in the
            two-lever drug-discrimination paradigm in rats trained to
            discriminate saline from LSD tartrate (0.08 mg/kg) and for the
            ability to displace <125I>-(R)-DOI
            (<125I>-(R)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane)
            from rat cortical homogenate 5-HT2 receptors.The compounds,
            1-(5-methoxy-2,3-dihydrobenzofuran-4-yl)-2-aminopropane
            (6a) and its 7-brominated analogue 6b, possessed activity
            comparable to their conformationally flexible counterparts
            1-(2,5-dimethoxyphenyl)-2-aminopropane (3) and its 4-bromo
            derivative DOB (5), respectively.The results suggest that the
            dihydrofuran ring in 6a and 6b models the active conformation
            of the 5-methoxy groups in 3 and 5.Free energy of binding,
            derived from radioligand displacement KA values, indicated that
            addition of the bromine in either series contributes 2.4-3.2
            kcal/mol of binding energy.On the basis of surface area of the
            bromine atom, this value is 2-3 times higher than would be
            expected on the basis of hydrophobic binding.Thus,
            hydrophobicity of the para substituent alone cannot account for
            the dramatic enhancement of hallucinogenic activity.Although
            this substituent may play a minor role in orienting the
            conformation of the 5-methoxy group in derivatives such as 4
            and 5, there appears to be some other, as yet unknown, critical
            receptor interaction.
 CNR:
            5528140

 Author:
            Nichols, David E.; Brewster, William K.; Johnson, Michael P.;
            Oberlender, Robert; Riggs, Robert M.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 33, 2, 1990, 703-710
 Title:
            Nonneurotoxic Tetralin and Indian Analogues of
            3,4-(Methylenedioxy)amphetamine (MDA)
 Abstract:
            Four cyclic analgues of the psychoactive phenethylamine
            derivative 3,4-(methylenedioxy)amphetamine were
            studied.These congeners, 5,6- and
            4,5-(methylenedioxy)-2-aminoindan (3a and 4a, respectively),
            and 6,7- and 5,6-(methylenedioxy)-2-aminotetralin (3b and 4b,
            respectively) were tested for stimulus generalization in the
            two-lever drug-discrimination paradigm.Two groups of rats
            were trained to discriminate either LSD tartrate (0.08 mg/kg)
            from saline, or (+/-)-MDMA*HCl (1.75 mg/kg) from saline.In
            addition, a 2-aminoindan (5a) and 2-aminotetralin (5b) congener
            of the hallucinogenic amphetamine
            1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM)
            were also evaluated.None of the methylenedioxy compounds
            substituted in LSD-trained rats, while both 3a and 3b fully
            substituted in MDMA-trained rats.Compounds 4a and 4b did
            not substitute in MDMA-trained rats.Compounds 5a and 5b did
            not substitute in MDMA-trained rats, although 5a substituted in
            LSD-trained rats, but with relatively low potency compared to
            its open-chain counterpart.In view of the now well-established
            serotonin neurotoxicity of 3,4-(methylenedioxy)amphetamine
            and its N-methyl homologue 1, 3a and 3b were evaluated and
            compared to 1 for similar toxic effects following a single acute
            dose of 40 mg/kg sc.Sacrifice at 1 week showed that neither 3a
            nor 3b depressed rat cortical or hippocampal 5-HT or 5-HIAA
            levels nor were the number of binding sites (Bmax) depressed
            for <3H>paroxetine.By contrast, and in agreement with other
            reports, 1 significantly depressed all three indices of
            neurotoxicity.These results indicate that 3a and 3b have acute
            behavioral pharmacology similar to 1 but that they lack similar
            serotonin neurotoxicity.
 CNR:
            5500562


 Author:
            Koreeda, Masato; Brown, Lindsey; Valdes, Leander J.
 Reference:
            Journal, CMLTAG, Chem.Lett., EN, 11, 1990, 2015-2018
 Title:
            The Absolute Stereochemistry of Salvinorins
 Abstract:
            The absolute stereostructures of the hallucinogenic diterpenes
            salvinorin A and B have been unambiguously determined by
            the use of the non-empirical exciton chirality circular dichroism
            method on their 1a,2a-diol dibenzoate derivative.
 CNR:
            5540409

 Author:
            Kusano, Genjiro; Koike, Yutaka; Inoue, Hideo; Nozoe, Shigeo
 Reference:
            Journal, CPBTAL, Chem.Pharm.Bull., EN, 34, 8, 1986,
            3465-3470
 Title:
            The Constituents of Gymnopilus spectabilis
 Abstract:
            Cerevisterol (1) and a new acetylenic compound,
            4,6-decadiyne-1,3,8-triol (2) were isolated and characterized
            from a hallucinogenic mushroom, Gymnopilus spectabilis (FR.)
            A.H.SMITH, along with ergosterol, ergosteryl peroxide and
            choline.Psychoactive compounds such as psilocybin and related
            compounds have not been detected in our collections of this
            mushroom, though some psilocybin has been found in several
            other Japanese mushrooms.Keywords - Gymnopilus spectabilis;
            hallucinogenic mushroom; cerevisterol;
            4,6-decadiyne-1,3,8-triol; ergosterol; ergosteryl peroxide;
            choline
 CNR:
            5674541

 Author:
            Houghton, Peter J.; Lian, Lu Ming
 Reference:
            Journal, PYTCAS, Phytochemistry, EN, 25, 8, 1986, 1907-1912
 Title:
            IRIDOIDS, IRIDOID-TRITERPENOID CONGENERS AND
            LIGNANS FROM DESFONTAINIA SPINOSA
 Abstract:
            Key Word Index - Desfontainia spinosa; Loganiaceae; iridoids;
            seco-iridoids; triterpene-secoiridoids; desfontainic acid;
            desfontainoside; lignans; 7-O-(p-coumaroyl)-loganin;
            secoxyloganin; dimethyl secologanoside; sweroside;
            (+)-syringaresinol; liriodendrin; (+)-syringaresinol
            O-b-D-glucoside.The leaves of Desfontainia spinosa were
            found to contain the three known seco-iridoids secoxyloganin,
            dimethyl secologanoside and sweroside in addition to the three
            iridoids loganin, loganetin and loganic acid previously
            reported.In addition a novel derivative
            7-O-(p-coumaroyl)-loganin was isolated.The leaves were also
            found to contain a novel type of compound consisting of
            ester-linked triterpene and seco-iridoid congeners between
            24-hydroxytormentic acid and secoxyloganin.These were
            named desfontainic acid, a monoglucoside, and
            desfontainoside, the corresponding diglucoside.Desfontainoside
            only could be detected in the stems.The stem contained the
            same iridoids and also the known furofuran lignans
            (+)-syringaresinol, (+)-syringaresinol O-b-D-glucopyranoside
            and liriodendrin.The iridoids present provide chemotaxonomic
            evidence for retaining Desfontainia in the Loganiaceae as a
            separate tribe the Desfontaineae.None of the compounds
            present forms a basis for the reputed hallucinogenic activity.
 CNR:
            5858446

 Author:
            Repke, David B.; Grotjahn, Douglas B.; Shulgin, Alexander T.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 28, 7, 1985, 892-896
 Title:
            Psychotomimetic N-Methyl-N-isopropyltryptamines. Effects of
            Variation of Aromatic Oxygen Substituents
 Abstract:
            Eight N-methyl-N-isopropyltryptamines (MIPTs) possessing
            various aromatic oxygen substituents were prepared,
            characterized, and evaluated for hallucinogenic activity in
            man.In at least two instances (the Ar H and the Ar 5-OCH3, 1
            and 4) the unsymmetrical nitrogen substitution led to a
            substantial increase in potency as well as oral activity when
            compared to the symmetrical dimethyl
            homologues.Qualitatively,
            4-hydroxy-N-methyl-N-isopropyltryptamine (2) was the most
            interesting in overall effect, producing a classic hallucinogenic
            profile.The 5-methoxy congeger 4 resulted in a state
            characterized by heightened conceptual stimulation lacking in
            visual phenomena.Other members of the series exhibited
            diminished effects.
 CNR:
            5745031

 Author:
            Kawanishi, K.; Uhara, Y.; Hashimoto, Y.
 Reference:
            Journal, PYTCAS, Phytochemistry, EN, 24, 6, 1985, 1373-1376
 Title:
            ALKALOIDS FROM THE HALLUCINOGENIC PLANT
            VIROLA SEBIFERA
 Abstract:
            Key Word Index - Virola sebifera; Myristicaceae;
            hallucinogenic plant; alkaloids; N-methyl-N-acetyltryptamine;
            N-methyl-N-formyltryptamine;
            2-methyl-1,2,3,4-tetrahydro-b-carboline;
            N,N-dimethyltryptamine; N,N-dimethyltryptamine-N-oxide;
            N-monomethyltryptamine. - Bark of Virola sebifera used in the
            preparation of hallucinogenic snuffs and drinks in Venezuela
            has yielded N-methyl-N-formyltryptamine and
            N-methyl-N-acetyltryptamine, which exist in two rotameric
            forms reflecting hindered rotation around the carbon-nitrogen
            bond of the amide function.They were detected by HPLC as
            well as NMR. 2-Methyl-1,2,3,4-tetrahydro-b-carboline,
            N,N-dimethyltryptamine, its oxide and
            N-monomethyltryptamine were also identified.
 CNR:
            5827194

 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:
            Nichols, David E.; Jadhav, Kiran P.; Oberlender, Robert A.;
            Zabik, Joseph E.; Bossart, Josef F.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 27, 9, 1984, 1108-1111
 Title:
            Synthesis and Evaluation of Substituted
            2-Phenylcyclobutylamines as Analogues of Hallucinogenic
            Phenethylamines: Lack of LSD-like Biological Activity
 Abstract:
            cis- and trans-2-(2,4,5-trimethoxyphenyl)cyclobutylamine and
            trans-2-(2,5-dimethoxy-4-methylphenyl)cyclobutylamine were
            synthesized as conformationally restricted analogues of
            hallucinogenic phenylisopropylamines.In rats trained to
            discriminate saline from LSD (0.08 mg/kg, ip) in a two-lever
            drug discrimination paradigm, no generalization of the LSD
            stimulus to the cis trimethoxy compound occurred at doses up to
            20 mg/kg.For both of the trans compounds, partial
            generalization of the LSD cue occurred at doses of 5 mg/kg or
            greater.In contrast, complete generalization occurred with
            trans-2-(2,5-dimethoxy-4-methylphenyl)cyclopropylamine.The
            ED 50 for this compound and the doses of the trans cyclobutyl
            homologues at which significant drug-appropriate responding
            occurred indicate that the latter are on the order of 50-75 times
            less potent than the cyclopropylamine analogue.The lack of the
            generalization to the cyclobutylamines indicates either that their
            discriminative stimulus properties differ from LSD or that they
            lack discriminative effects.
 CNR:
            5747974

 Author:
            Ferguson, P. W.; Keller, W. J.; Risinger, F. O.
 Reference:
            Journal, JPMSAE, J.Pharm.Sci., EN, 73, 5, 1984, 692-693
 Title:
            <14C>Normacromerine Fate in the Rat
 Abstract:
            The biological fate of <14C>normacromerine, a dimethoxylated
            phenylethylamine derivative with putative hallucinogenic
            properties, was evaluated in male Sprague-Dawley rats at 100
            mg/kg po.Urine was the primary elimination route accounting
            for 50percent of administeres carbon-14 after 24 h.Of this urine
            radioactivity, normacromerine comprised 30percent at 8 h
            decreasing to nondetectable levels at 24 h.Cabron-14 in feces
            represented <10percent of the administered dose at 24 h, and
            14CO2 expiration was not detected.Studies of normacromerine
            fate in comparison with previously studied phenethylamines
            may enhance evaluation of hallucinogenic potential of
            normacromerine.
 CNR:
            5837546


 Author:
            Nozoe, Shigeo; Koike, Yutaka; Tsuji, Emi; Kusano, Genjiro;
            Seto, Haruo
 Reference:
            Journal, TELEAY, Tetrahedron Lett., EN, 24, 16, 1983,
            1731-1734
 Title:
            ISOLATION AND STRUCTURE OF GYMNOPRENOLS, A
            NOVEL TYPE OF POLYISOPRENEPOLYOLS FROM
            GYMNOPILUS SPECTABILIS
 Abstract:
            Gymnoprenols, a novel type polyisoprenepolyols, have been
            isolated from the fruiting body of an hallucinogenic mushroom,
            Gymnopilus spectabilis.The structures of these polyols which
            occur as a mixture of isoprene homologues have been
            elucidated by chemical degradations and spectroscopic
            analyses.
 CNR:
            5550181


 Author:
            Nozoe, Shigeo; Koike, Yutaka; Kusano, Genjiro; Seto, Haruo
 Reference:
            Journal, TELEAY, Tetrahedron Lett., EN, 24, 16, 1983,
            1735-1736
 Title:
            STRUCTURE OF GYMNOPILIN, A BITTER PRINCIPLE
            OF AN HALLUCINOGENIC MUSHROOM,
            GYMNOPILUS SPECTABILIS
 Abstract:
            Structure of gymnopilin (1), a bitter principle of an
            hallucinogenic mushroom Gymnopilus spectabilis, was
            elucidated by chemical degradation and spectroscopic methods.
 CNR:
            5550182

 Author:
            Repke, David B.; Ferguson, Wilfred J.
 Reference:
            Journal, JHTCAD, J.Heterocycl.Chem., EN, 19, 1982, 845-848
 Title:
            Psilocin Analogs. III. Synthesis of 5-Methoxy- and
            5-Hydroxy-1,2,3,4-tetrahydro-9H-pyrido<3,4-b>indoles
 Abstract:
            A number of tetrahydro-b-carbolines were prepared with
            oxygen substituents at C-5.This class of compounds represents
            a hybrid between two naturally occuring groups of
            hallucinogenic molecules, the 4-hydroxyptryptamines and the
            6- and 7-oxygenated b-carbolines.
 CNR:
            5566103

 Author:
            Nichols, David E.; Lloyd, David H.; Hoffman, Andrew J.;
            Nichols, Maxine B.; Yim, George K. W.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 25, 5, 1982, 530-535
 Title:
            Effects of Certain Hallucinogenic Amphetamine Analogues on
            the Release of <3H>Serotonin from Rat Brain Synaptosomes
 Abstract:
            The enantiomers of 3,4-(methylenedioxy)amphetamine
            (MDA), p-methoxyamphetamine (PMA), and N-Me-MDA
            (MDMA), along with their a,a-dimethylated derivatives, were
            evaluated for an effect on the release of <3H>serotonin from
            rat whole brain synaptosomes.The amphetamine isomers were
            all potent in inducing the release of <3H>serotonin at bath
            concentrations of 1 and 10 mM but were inactive at 0.1 mM.No
            significant difference in isomer potency was observed at the
            10-mM concentration.However, at 1 mM the (+) isomer of
            MDMA was more effective in inducing release than was the (-)
            isomer.Since it is the (+) isomer which is clinically active, this
            result suggests that transmitter release may play a role in the
            biological activity of MDMA.By contrast, the a,a-dimethyl
            compounds were not effective in releasing serotonin, even at
            the highest bath concentration.
 CNR:
            5639868

 Author:
            Kline, Toni B.; Benington, Frederick; Morin, Richard D.;
            Beaton, John M.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 25, 8, 1982, 908-913
 Title:
            Structure-Activity Relationships in Potentially Hallucinogenic
            N,N-Dialkyltryptamines Substituted in the Benzene Moiety
 Abstract:
            A series of N,N-dialkyltryptamines with methylthio or
            methylenedioxy substituents in the 4, 5, and 6 positions and
            methyl or isopropyl on the side-chain nitrogen has been
            synthesized.The behavioral pharmacology of these compounds
            showed them to posses Bovet-Gatti profiles characteristic of
            hallucinogens, and the 5-methylthio congener was the most
            potent.Binding studies at <3H>LSD and <3H>5-HT sites
            demonstrated that no single structural feature correlated with
            binding or behavioral changes and suggest a complex mode of
            action for these potential hallucinogenic agents.
 CNR:
            5640239

 Author:
            Kline, Toni B.; Benington, Frederick; Morin, Richard D.;
            Beaton, John M.; Glennon, Richard A.; et al.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 25, 11, 1982,
            1381-1383
 Title:
            Structure-Activity Relationships for Hallucinogenic
            N,N-Dialkyltryptamines: Photoelectron Spectra and Serotonin
            Receptor Affinities of Methylthio and Methylenedioxy
            Derivatives
 Abstract:
            Serotonin receptor affinity and photoelectron spectral data were
            obtained on a number of substituted
            N,N-dimethyltryptamines.Evidence is presented that
            electron-donating substituents in the 5-position lead to
            enhanced behavioral disruption activity and serotonin receptor
            affinity as compared to unsubstituted N,N-dimethyltryptamine
            and analogues substituted in the 4- or 6-position.Some
            correlation was found between ionization potentials and
            behavioral activity, which may have implications concerning
            the mechanism or receptor binding.
 CNR:
            5701067

 Author:
            Bindal, M. C.; Singh, P.; Gupta, S. P.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 32, 7, 1982, 719-721
 Title:
            Structure-Activity Studies on Hallucinogenic
            Phenylalkylamines Using Fujita-Ban Approach
 Abstract:
            The nature of the substituents and their contribution at different
            ring positions to the overall hallucinogenic activity in a series of
            phenylalkylamines (amphetamines) are studied by using
            Fujita-Ban additive model.The calculated activity contributions
            of substituents and of parent structure, respectively, are then
            utilized to predict the most potent compound in the series and to
            remove the uncertainties in the observed activity of some
            phenylalkylamines.The most potent compound predicted is
            2,6-dimethoxy-4-bromophenylisopropylamine. - Key words:
            Amphetamines .Fujita-Ban model .Hallucinogens
            .Phenylalkylamines .Structure-activity relationship
 CNR:
            5734401

 Author:
            Gupta, S. P.; Bindal, M. C.; Singh, P.
 Reference:
            Journal, ARZNAD, Arzneim.Forsch., EN, 32, 10, 1982,
            1223-1225
 Title:
            Quantitative Structur-Activity Studies on Hallucinogenic
            Mescaline Analogs Using Modified First Order Valence
            Connectivity
 Abstract:
            Attempt is made to correlate the hallucinogenic activity of a
            series of mescaline analogs with Kier's molecular connectivity
            index (c).In order to find a simpler and more meaningful
            correlation, a little modification is sugested to the first-order
            valence connectivity index (1cv).The modification is found to
            reveal utterly simple but significant correlations between
            activity and 1cv, which could describe the structural influence
            on the activity more vividly. - Key words: Hallucinogens
            .Mescaline, analogs, molecular connectivity, structure-activity
            relationship .Phenethylamine, analogs
 CNR:
            5797170

 Author:
            Gupta, S. P.; Singh, P.; Bindal, M. C.
 Reference:
            Journal, FRPSAX, Farmaco Ed.Sci., EN, 37, 8, 1982, 566-570
 Title:
            QSAR STUDIES ON PHENYLALKYLAMINES
            INTERACTING WITH THE SEROTONIN RECEPTOR
 Abstract:
            An attempt is made to analyse the serotonin receptor binding
            affinity (pD2) of a small series of hallucinogenic
            phenylalkylamines in relation to various physical and
            physico-chemical parameters.It is found that pD2 can be
            significantly correlated with steric parameters, such as van der
            Waals (Vw) and molar refraction (MR).Based on the correlation
            equations obtained, it is suggested that the hallucination might
            be related with binding of drug with the serotonin receptor and
            that such binding might involve a van der Waals type of
            interaction.
 CNR:
            5937577

 Author:
            Kothari, Paresh J.; Hathaway, Bruce A.; Nichols, David E.;
            Yim, George K. W.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 24, 7, 1981, 882-884
 Title:
            Synthesis and Serotonin-like Activity of
            2-Amino-5,8-dimethoxy-6-methyl-1,2-dihydronaphthalene
 Abstract:
            As a new type of rigid analogue for hallucinogenic
            phenethylamines,
            2-amino-5,8-dimethoxy-6-methyl-1,2-dihydronaphthalene was
            synthesized.Evaluation in the rat fundus preparation showed it
            to be a much weaker serotonin agonist than its
            1,2,3,4-tetrahydro homologue.Both the dihydro and tetrahydro
            compounds were able to elicit the serotonin syndrome in rats,
            but with the dihydro compound also appearing weaker in this
            assay.Both rigid analogues were less potent than the known
            halucinogen
            1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM).
 CNR:
            5637668

 Author:
            Sobel, Yves; Mercier, Christiane; Dubois, Jaques-Emile
 Reference:
            Journal, EJMCA5, Eur.J.Med.Chem.Chim.Ther., FR, 16, 5,
            1981, 477-479
 Title:
            Methode DARC/PELCO: QSAR de phenylalkylamines
            methoxylees hallucinogenes
 Abstract:
            The hallucinogenic activity of phenylalkylamines in man has
            previously been treated in QSARs either based on limited
            populations or non-significant or difficult to interpret.It can now
            be handled by a single QSAR which accounts for the 46 activity
            data reported in the literature by means of three structural
            variables.These variables are detected as being the most
            significant from the study of 35 structures and associated data of
            comparable precision.
 CNR:
            5673859

 Author:
            Ahmed, F. R.; Huber, C. P.
 Reference:
            Journal, ACBCAR, Acta Crystallogr.Sect.B, EN, 37, 1981,
            1874-1877
 Title:
            Structure of 1-Phenylcyclohexanol
 Abstract:
            C12H16O, a precursor to the hallucinogenic drug
            1-phenylcyclohexylamine, is monoclinic, P21/c, a=20.605(3),
            b=10.657(2), c=19.683(3) Angstroem, b=100.75(1) deg, Z=16,
            Mr=176.26, Do=1.101, Dc=1.103 Mg m-3; R=0.049 and
            Rw=0.052 for 4619 observed reflexions.The cyclohexane ring
            is in the chair form.The hydroxyl group is axial and the phenyl
            group equatorial, but the twist of the phenyl ring around the
            adjoining bond varies through a wide range <ca. 39 (1) deg> in
            the four independent molecules.Four intermolecular O-H...O
            bonds, forming a closed loop, link the independent molecules
            into a tetramer while the tetramers are held together only by
            van der Waals forces.On short exposure to X-rays, the crystals
            sublime gradually, disappearing completely within a period of
            two to four days.
 CNR:
            5679049

 Author:
            Gupta, S. P.; Singh, P.; Bindal, M. C.
 Reference:
            Journal, EJMCA5, Eur.J.Med.Chem.Chim.Ther., EN, 16, 5,
            1981, 446-448
 Title:
            STRUCTURE-ACTIVITY STUDIES ON LSD ANALOGS
            USING VAN DER WAALS VOLUME
 Abstract:
            The anti-serotonin and hallucinogenic activities of LSD analogs
            are analysed in relation to van der Waals volume (Vw).Both the
            activities are found to be significantly related with Vw, and it is
            observed from the relating equations that, for both the activities,
            the substitution in the side chain is more important than in the
            ring and that the bigger substituent will lead to the increased
            activities.Using the appropriate relating equations, the two
            activities are predicted for some more compounds belonging to
            studied series.
 CNR:
            5721362

 Author:
            Harris, R. Adron; Homfeld, Enno; Campaigne, E.
 Reference:
            Journal, JPPMAB, J.Pharm.Pharmacol., EN, 33, 1981, 320-322
 Title:
            Sturucture-activity relationships among hallucinogenic
            tryptamine derivatives evaluated by schedule-controlled
            behaviour
 Abstract:
 CNR:
            5807277

 Author:
            Standridge, Robert T.; Howell, Henry G.; Tilson, Hugh A.;
            Chamberlain, John H.; Holava, Henry M.; et al.
 Reference:
            Journal, JMCMAR, J.Med.Chem., EN, 23, 2, 1980, 154-162
 Title:
            Phenylalkylamines with Potential Psychotherapeutic Utility. 2.
            Nuclear Substituted 2-Amino-1-phenylbutanes
 Abstract:
            A series of
            2-amino-1-(4-substituted-2,5-dimethoxyphenyl)butanes (Table
            V) was prepared as analogues of
            (R)-2-amino-1-(2,5-dimethoxy-4-methylphenyl)butane (1a).
            1-(2,5-Dimethoxyphenyl)-2-(N-phthalimido)butane (7) was
            utilized as a synthetic intermediate common to many of the
            target compounds.Animal data are presented indicating that
            most of these analogues have low hallucinogenic
            potential.Selected compounds were compared with 1a in an
            avoidance-responce acquisition model which differrentiates
            between 1a and the human hallucinogens DOM (2a) and
            DOET (2b).Structure-activity relationships of these analogues
            are discussed.
 CNR:
            5891032
