@article {HARBERT38, author = {CHARLES A. HARBERT and JACOB J. PLATTNER and WILLARD M. WELCH and ALBERT WEISSMAN and B. KENNETH KOE}, title = {Neuroleptic Activity of the 5-Aryltetrahydro-γ-carboline Series Conformational Requirements for Interaction with Central Dopamine Receptors}, volume = {17}, number = {1}, pages = {38--42}, year = {1980}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {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.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/17/1/38}, eprint = {https://molpharm.aspetjournals.org/content/17/1/38.full.pdf}, journal = {Molecular Pharmacology} }