TY - JOUR T1 - Neuroleptic Activity of the 5-Aryltetrahydro-γ-carboline Series Conformational Requirements for Interaction with Central Dopamine Receptors JF - Molecular Pharmacology JO - Mol Pharmacol SP - 38 LP - 42 VL - 17 IS - 1 AU - CHARLES A. HARBERT AU - JACOB J. PLATTNER AU - WILLARD M. WELCH AU - ALBERT WEISSMAN AU - B. KENNETH KOE Y1 - 1980/01/01 UR - http://molpharm.aspetjournals.org/content/17/1/38.abstract N2 - A series of novel 5-aryltetrahydro-γ-carboline neuroleptics is described. Their interaction with the dopamine receptor is demonstrated by their potent and long-lasting blockade of amphetamine-induced stereotyped behavior in rats and by the displacement of bound 3H-spiroperidol in vitro. The 5-aryl-γ-carboline nucleus appears to be primarily responsible for receptor interaction while the side chain serves to extend duration, presumably by altering metabolism and/or tissue distribution. The conformation of the semirigid 5-aryl-γ-carboline nucleus approximates that of the previously proposed active conformation of the open-chain diphenylbutylpiperidine neuroleptics. Comparison of the crystal structure of CP-36,584 with those of apomorphine and (+)-dexclamol suggests a common, conformationally restricted phenethylamine moiety as the species interacting with the receptor. Findings with the γ-carboline neuroleptics coalesce previously disparate proposals for the dopamine receptor interactions of butaclamol, diphenylbutylamines, and piperidylidene thioxanthenes. ER -