N-Alkyl derivatives of (.+-.)-.alpha.-methyldopamine

Abstract

A series of N-alkylated .alpha.-methyldopamine derivatives was prepared for comparison of their biological effects with those of semirigid dopamine congeners derived from 2-aminotetralin systems. All .alpha.-methyldopamine derivatives were inert as dopaminergic agonists in a variety of animal assays, both centrally and peripherally. Certain compounds produced powerful and prolonged locomotor hyperactivity on intra-accumbens injection in mice, by indirect mechanism(s). A rationalization based upon conformational analysis is presented for the lack of direct dopaminergic agonist activity of .alpha.-methyldopamine derivatives.