Normal MPTP binding in parkinsonian substantial nigra: evidence for extraneuronal toxin conversion in human brain

Abstract

MPTP (N-methyl-4 phenyl-1,2,3,6 tetrahydropyridine) is a neurotoxin that induces a parkinsonian syndrome. 3H-MPTP binds densely to substantia nigra specimens from neurologically normal brains. It binds just as densely to specimens from patients with idiopathic parkinsonism despite substantial losses of dopaminergic neurons in this disorder. These results accord with findings in animal studies that suggest that MPTP binds to an extraneuronal enzyme, monoamine oxidase, which converts it to a toxic metabolite that is actively taken up and accumulates inside dopaminergic neurons. An MPTP-like toxin has been postulated to be a possible cause of idiopathic parkinsonism. Preventing uptake and concentration could be one means of blocking the action of such a toxin.