Synthesis and central dopaminergic effects of N-(4,6-dimethyl-2-pyridinyl)benzamides.

N-(4,6-Dimethyl-2-pyridinyl)benzamides 1-24 and the corresponding tertiary derivatives 29-33 were synthesized and studied for possible dopamine-inhibitory properties by testing their effect on motility of naive and reserpinized mice. Unlike the orthopramides, they failed to show any antidopaminergic properties, but some of the secondary derivatives showed instead effects of postsynaptic dopaminergic agonism. The latter compounds were subsequently studied for their effects on apomorphine reversal of reserpine-induced akinesia and on cerebral HVA levels in rats. Contraversive circling induced by compound 11 in 6-hydroxydopamine-lesioned mice suggests that a direct mechanism was involved.