The catecholamine uptake blocker nomifensine protects against MPTP-induced parkinsonism in monkeys.

Administration of MPTP (1-methyl-1,2,3,6-tetrahydropyridine) to Macaca fascicularis monkeys produced severe parkinsonism (hypokinesia, tremor, rigidity, aphagia, adipsia) and more than 90% loss of nigral dopamine neurons, striatal dopamine content and striatal 3H-mazindol binding. Treatment with the catecholamine uptake blocker nomifensine counteracted the behavioral, histological and neurochemical effects induced by MPTP. For obtaining best protection, nomifensine had to be administered for weeks after MPTP. The results suggest that the selective target-directed neurotoxic action of MPTP on dopamine neurons in monkeys is mediated via the dopamine uptake mechanism.