Pargyline Prevents MPTP-Induced Parkinsonism in Primates

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin which produces permanent parkinsonism in human and nonhuman primates. Treatment of squirrel monkeys with pargyline, a monoamine oxidase (MAO) inhibitor, prevents both clinical and neuropathological evidence of the neurotoxic effects of MPTP. Pargyline also inhibits conversion of MPTP to 1-methyl-4-phenylpyridinium ion (MPP$^{+}$), a metabolic step that occurs rapidly after administration of MPTP in animals not treated with pargyline. It is proposed that the conversion of MPTP to MPP$^{+}$, possibly involving MAO, may be important for the neurotoxic effects of MPTP to take place, and MPTP itself may not be the neurotoxic agent.