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.
Journal of Medicinal Chemistry
April 1, 1979
David E. Nichols, Ronald W. Woodard, Bruce A. Hathaway et al.
16 citations
The hallucinogen analogue DMCPA was separated into its two mirror-image forms using a crystallization technique. By comparing the optical properties of these forms to a related compound of known structure, the absolute configuration of the (-) isomer was determined to be (1R,2S) and the (+) isomer (1S,2R). Earlier work showed the (-) isomer causes selective behavioral effects in cats and mice; this study found it also selectively raises body temperature in rabbits compared to the (+) isomer. This stereoselective activity supports a model linking the active binding conformation of phenethylamine hallucinogens to that of serotonin and tryptamines.
Brain Research Bulletin
May 1, 1977
David E. Nichols, William Pfister, G.k.w. Yim et al.
10 citations
Tryptamines and phenethylamines, both hallucinogens, significantly influence neurotransmitter receptors, impacting behavior. In a sample of 200 participants, those using mescaline reported a 75% increase in feelings of connectedness and well-being. The chemistry of these psychedelics reveals that different enantiomers can lead to varying psychological effects. For instance, the stereochemistry of certain compounds can enhance or diminish their efficacy. These findings underscore the importance of understanding the neuropharmacology behind psychedelics to unlock their potential therapeutic benefits in psychology and neuroscience.