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

A series of N-alkylated alpha-methyldopamine derivatives has been prepared for comparison of their biological effects with those of semirigid dopamine congeners derived from 2-aminotetralin systems. All of the alpha-methyldopamine derivatives were inert as dopaminergic agonists in a variety of animal assays, both centrally and peripherally, although 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.