Printed in the U.S.A. LSD AND PHENE~~~AMTNE HALLUCINOGENS: NEW STRUCTURAL ANALOGY AND IMPLICATIONS FOR RECEPTOR GEOMETRY

The hallucinogen analog tram-2-(2,5-dimethoxy-4-methylphenyl)-cyclo-propylamiae (DMCPA) was resolved into its two optical isomers. Eaam-inatioa of selected behavioral, profiles in mice and cats clearly showed that the levorotatory isomer of DMCPA possesses atereoaelective acti-vity when compared with the dextro isomer. The results parallel those obtained using the isomers of the known hallucinogen, DOM (STP) in the same animal models. Comparison of the optical rotatory dispersion (ORD) curves for the N-(5-bromosalicylidene) derivatives of DMCPA and traps-2-pheaylcyclopropylamine (tranylcypromlne) of known absolute configuration established the configuration of DMCPA to be (-)-1R,2S. This stereo-selective activity and proof of absolute configuration lend strong support to a new model of the hallucinogen receptor. The proposed model suggests possible structural similarities between LSD and phen-ethylamine hallucinogens. Recently we proposed a new way to view the possible structural relation