PT  - JOURNAL ARTICLE
AU  - CHARLES A. HARBERT
AU  - JACOB J. PLATTNER
AU  - WILLARD M. WELCH
AU  - ALBERT WEISSMAN
AU  - B. KENNETH KOE
TI  - Neuroleptic Activity of the 5-Aryltetrahydro-γ-carboline Series Conformational Requirements for Interaction with Central Dopamine Receptors
DP  - 1980 Jan 01
TA  - Molecular Pharmacology
PG  - 38--42
VI  - 17
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/17/1/38.short
4100  - http://molpharm.aspetjournals.org/content/17/1/38.full
SO  - Mol Pharmacol1980 Jan 01; 17
AB  - 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.