Stimulation of a dopamine-sensitive adenylate cyclase in homogenates of rat striatum by a metabolite of piribedil (ET 495).

Abstract

The addition of dopamine (1–100μM) to homogenates of rat striatum incubated with ATP evoked a 120% increase in the rate of cyclic 3′5′ adenosine monophosphate (cyclic AMP) production. The effects of added dopamine were mimicked by the addition of the compound S 584 [1-3,4-(dihydroxybenzyl)-4-(2-pyrimidinyl) piperazine] (1–100 μM), a catechol metabolite of the dopaminergic stimulant drug piribedil (ET 495). The latter substance was itself inactive in this system at these concentrations. The stimulation of cyclic AMP production by dopamine and by S 584 was potently inhibited by the dopamine antagonist dru chlorpromazine and spiroperidol (1–10 μM). It is possible that the dopaminergic effects elicited by piribedil may be mediated through the active metabolite S 584.