Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents.
Life sciences – December 17, 1984
Source: PubMed
Summary
A striking correlation exists between the binding affinities of psychoactive agents for 5-HT2 receptors and their behavioral effects. In a sample of 22 substances, a strong relationship (r = 0.938) was observed between 5-HT2 binding affinities and ED50 values from stimulus generalization tests using DOM as the training drug. Additionally, among 15 agents with human data, another significant correlation (r = 0.924) linked 5-HT2 affinities to hallucinogenic potency, suggesting that these compounds primarily act through 5-HT2 receptor interactions.
Abstract
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.