Differential time course of protection by monoamine oxidase inhibition and uptake inhibition against MPTP neurotoxicity on central catecholamine neurons in mice.

Pretreatment with the monoamine oxidase inhibitor pargyline or the catecholamine uptake blocker nomifensine both protected central catecholamine neurons against MPTP-induced neurotoxicity as monitored by analyzing catecholamine levels and [3H]mazindol binding. Post-treatment with the inhibitors showed that the administration of nomifensine could be delayed longer than that of pargyline in order to achieve a protective effect. The results are compatible with the view that the monoamine oxidase-catalyzed conversion of MPTP to a toxic metabolite MPP+ occurs mainly extraneuronally. MPP+ is subsequently taken up and accumulated selectively in catecholamine neurons, initiating degeneration.