Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents.
The affinities (Ki values) of twenty two psycho-active agents, including LSD, 5-OMe DMT and a series of phenalkylamine derivatives, for cortical 5-HT1 and 5-HT2 binding sites were compared with two measures of behavioral activity. It was found that a significant correlation (r = 0.938) exists between the 5-HT2 binding affinities of these agents and their ED50 values as determined in tests of stimulus generalization using 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) as the training drug. Furthermore, for fifteen of these agents where human data were available, a significant correlation (r = 0.924) also exists between 5-HT2 binding affinities and their human hallucinogenic potencies. The results of this study suggest that the mechanism of action of these agents involves 5-HT2-related events.
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D006213:Hallucinogens / Q000494:pharmacology*; D006801:Humans; D008238:Lysergic Acid Diethylamide / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008732:Methoxydimethyltryptamines / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism / Q000502:physiology; D012701:Serotonin / Q000502:physiology*
D006213:Hallucinogens; D008732:Methoxydimethyltryptamines; D011985:Receptors, Serotonin; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D012701:Serotonin; D008238:Lysergic Acid Diethylamide