Potentiation and inhbition of some central actions of L(-)-dopa by decarboxylase inhibitors.

Abstract

DL-α-Methyl-α-hydrazino-3,4-dihydrophenylpropionlc acid (HMD) and [N1-(DL-seryl)-N2-(2,3,4-trihydroxybenzyl) hydrazine] (Ro 4-4602), two known inhibitors of aromatic amino acid decarboxylase (dopa decarboxylase), were investigated for their effect upon some centrally mediated actions of l-dopa. HMD enhanced the ability of l-dopa to increase motor activity and irritability in mice and to increase motor activity in rats. In addition, HMD enhanced the reversal by L-dopa of reserpine-induced hypothermia, suppression of locomotion and ptosis. Enhancement of the pharmacologic actions of L-dopa by HMD was associated with enhanced brain dopamine levels. In contrast, the vomiting response to L-dopa in dogs and pigeons was attenuated by treatment with HMD. Low doses of Ro 4-4602 (1-125 mg/kg) potentiated l-dopa reversal of the locomotor suppressant and ptotic actions of reserpine; whereas, high doses (125-625 mg/kg) inhibited these actions of L-dopa. It is concluded that decarboxylase inhibitors can either inhibit or potentiate the central actions of i.-dopa depending upon whether they reach the brain sites where L-dopa acts.