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Hallucinogenic drug interactions with neurotransmitter receptor binding sites in human cortex

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Abstract

The binding affinities of four hallucinogenic agents were analyzed at nine neurotransmitter binding sites in human cortex. d-Lysergic acid diethylamide (d-LSD), N,N-dimethyltryptamine (DMT), 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and 1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane (DOB) display highest affinity for the recently identified “DOB binding site” labeled by 77Br-R(-)DOB. The phenalkylamines, DOI and DOB, display subnanomolar affinity for the 77Br-R(-)DOB-labeled site, whereas the indolealkylamines, d-LSD and DMT, display nanomolar affinity for this site. d-LSD was the most potent of the four hallucinogens at six of the other eight sites analyzed in this study. All four hallucinogens also display high affinity for the 5-hydroxytryptamine2 (5-HT2) receptor subtype, with potencies ranging from 4 to 360 nM. Marked differences in relative affinities were observed between the indolealkylamines and the phenalkylamines at the 5-HT1A, 5-HT1D, and DOB binding sites. These rank-order differences in affinities are likely to account for the differing effects of these agents in various biochemical and physiological assays.

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Authors and Affiliations

  1. Department of Neurology and Pharmacology, Stanford University Medical Center, 94305, Stanford, CA, USA

    Pamela A. Pierce & Stephen J. Peroutka

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  1. Pamela A. Pierce
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  2. Stephen J. Peroutka
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Pierce, P.A., Peroutka, S.J. Hallucinogenic drug interactions with neurotransmitter receptor binding sites in human cortex. Psychopharmacology 97, 118–122 (1989). https://doi.org/10.1007/BF00443425

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  • DOI: https://doi.org/10.1007/BF00443425

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