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Andrew J. Hoffman

3 papers in the library · 268 citations · publishing 1982-1988

Papers

Effects of certain hallucinogenic amphetamine analogs on the release of [3H]-serotonin from rat brain synaptosomes

Journal of Medicinal Chemistry May 1, 1982 David E. Nichols, David Harley Lloyd, Andrew J. Hoffman et al. 178 citations

The enantiomers of MDA, PMA, and MDMA, along with their alpha,alpha-dimethylated derivatives, were tested for their ability to release serotonin from rat whole brain synaptosomes. At bath concentrations of 1 and 10 micrometers, the amphetamine isomers potently induced serotonin release, but were inactive at 0.1 micrometers. At 1 micrometer, the (+) isomer of MDMA was more effective than the (-) isomer, and because the (+) isomer is the clinically active form, this suggests that transmitter release may contribute to MDMA's biological activity. The alpha,alpha-dimethyl compounds did not release serotonin even at the highest concentration.

DOI: 10.1021/jm00347a010 MDMA Citation Amphetamine Computer science +2

Synthesis and serotonin receptor affinities of a series of enantiomers of .alpha.-methyltryptamines: evidence for the binding conformation of tryptamines at serotonin 5-HT1B receptors

Journal of Medicinal Chemistry July 1, 1988 David Nichols, D. H. Lloyd, Michael P. Johnson et al. 46 citations

A new method produces pure mirror-image forms of alpha-methyltryptamines (AMTs) from substituted indoles. The key step uses reductive amination with pure enantiomers of alpha-methylbenzylamine, followed by chromatographic separation and catalytic N-debenzylation. Optical purity was confirmed by chiral HPLC. Affinities of the AMT enantiomers were measured at 5-HT2 and 5-HT1B serotonin receptor subtypes in rat frontal cortex homogenates. Enantioselectivity depended on aromatic substituents: for 5-hydroxy or 5-methoxy, the S enantiomer had higher or equal affinity compared to the R enantiomer. For 4-oxygenated AMTs, this selectivity reversed, and 4-hydroxy or 4-methoxy did not improve affinity over unsubstituted compounds. The results suggest a binding conformation where the ethylamine side chain is trans and perpendicular to the indole ring plane.

DOI: 10.1021/jm00402a026 Serotonin Enantiomer Tryptamines Stereochemistry +5

Synthesis and LSD-like discriminative stimulus properties in a series of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives

Journal of Medicinal Chemistry September 1, 1985 Andrew J. Hoffman, David E. Nichols 44 citations

A series of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives was synthesized and tested in rats trained to discriminate LSD from saline. The N(6)-ethyl and -allyl derivatives were 2–3 times more potent than LSD itself, the N(6)-propyl was equally potent, the isopropyl derivative was half as active, and the n-butyl compound was 10 times less potent. No substitution occurred for norlysergic acid N,N-diethylamide or the N(6)-2-phenethyl derivative. These structure-activity relationships resemble those of certain serotonin and dopamine agonists.

DOI: 10.1021/jm00147a022 Lysergic acid diethylamide Alkyl Stimulus control Discriminative model +1