STUDIES ON THE MECHANISM OF ACTION OF AMANTADINE

The effect of amantadine hydrochloride on various aspects of catecholamine metabolism in the rat brain has been investigated. Amantadine failed to have any significant effect on brain concentrations of dopamine or noradrenaline even when administered daily for 9 days. Amantadine had no effect on the rate of decline of noradrenaline and dopamine concentrations after α‐methyl‐ p ‐tyrosine. In vitro , amantadine inhibited dopamine uptake into synaptosomes only at high concentrations, and caused little release of dopamine from synaptosomes. There is no evidence from these results to suggest that the anti‐Parkinsonian effect of amantadine is related to an action on dopaminergic mechanisms.