Hallucinogenic drug interactions with neurotransmitter receptor binding sites in human cortex.
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.
Pierce
P A
PA
Department of Neurology, Stanford University Medical Center, CA 94305.
Peroutka
S J
SJ
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D001967:Bromine Radioisotopes; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D006213:Hallucinogens / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D004130:N,N-Dimethyltryptamine / Q000494:pharmacology; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000378:metabolism
D000662:Amphetamines; D001967:Bromine Radioisotopes; D006213:Hallucinogens; D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; C003943:2,5-dimethoxy-4-bromoamphetamine; D008238:Lysergic Acid Diethylamide; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D004130:N,N-Dimethyltryptamine