Metabolism of the neurotoxic tertiary amine, MPTP, by brain monoamine oxidase.

The neurotoxic chemical MPTP (1-methyl-4-phenyl-1,2,4,5-tetrahydropyridine) is metabolized by rat brain mitochondrial fractions at a rate of 0.91 +/- 0.02 nmoles/mg protein/min. The major metabolite has been identified as the 1-methyl-4- phenylpyridinium species. This biotransformation process is blocked by 10(-7) M deprenyl and pargyline. MPTP itself inhibited the metabolism of benzylamine by brain mitochondrial fractions. These results are discussed in terms of possible bioactivation mechanisms that may be associated with the neurodegenerative properties of MPTP .