Mapping the dopamine receptor. 1. Features derived from modifications in ring E of the neuroleptic butaclamol

Abstract

Several analogs of the neuroleptic agent butaclamol, having modifications in the ring E region of the molecule were synthesized. Pharmacological evaluation identified 2 analogs equipotent to butaclamol, anhydrobutaclamol and deoxybutaclamol. The molecular structures of both the active and inactive analogs were analyzed and the results were used for mapping the central dopamine receptor. The existence of a previously proposed lipophilic accessory binding site on the receptor macromolecule was confirmed. Its minimum dimensions and its locus with respect to the primary binding sites were defined. A receptor model incorporating the above features is proposed.