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Hallucinogenic drug interactions with neurotransmitter receptor binding sites in human cortex.

P A Pierce, S J Peroutka

Psychopharmacology 1989 DOI: 10.1007/bf00443425 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics In vitro binding affinity study Peer reviewed
Population Human cortex tissue
Interventions d-Lysergic acid diethylamide (d-LSD) N N-dimethyltryptamine (DMT) 1-(2 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) 5-dimethoxy-4-bromophenyl)-2-aminopropane (DOB)
Key points All four hallucinogens bound most strongly to the "DOB binding site" labeled by 77Br-R(-)DOB, with DOI and DOB in the subnanomolar range and d-LSD and DMT in the nanomolar range. d-LSD was the most potent at six of the other eight sites, and all four bound the 5-HT2 receptor with potencies of 4 to 360 nM. The authors propose that these affinity differences account for the agents' differing effects in biochemical and physiological assays.

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.