1-Methyl-4-phenylpyridine is neurotoxic to the nigrostriatal dopamine pathway

Abstract
Systemic administration of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) is neurotoxic to cerebral dopaminergic neurones in several animal species, and can cause parkinsonism in man1–5. The mechanism of this action may be indirect. MPTP is oxidized in the brain to a pyridinium species, l-methyl-4-phenylpyridine (MPP+)6. This oxidation is greatly decreased by inhibition of monoamine oxidase B6, as are the biochemical effects of MPTP in the mouse7 and its neurotoxicity in the monkey8. We now show that MPP+ exerts a powerful neurotoxic action on the nigrostriatal dopamine system of the rodent.