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1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its oxidized metabolite 1-methyl-4-phenylpyridine (MPP+) produce a rapid depletion of intracellular ATP in isolated rat hepatocytes. This effect was dose-dependent and was consistently observed before the onset of toxicity. The monoamine oxidase inhibitor pargyline provided significant protection against MPTP-induced cell death and ATP loss, but had no effect with MPP+. Thus, ATP depletion may play a critical role in MPTP toxicity, possibly via the metabolic production of MPP+.
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