Dopamine uptake blockers protect against the dopamine depleting effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse striatum

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a recently described neurotoxin, produces a marked dopamine (DA) depletion in the mouse striatum. In this study, a series of DA uptake blockers was tested for their ability to prevent this effect of MPTP. The agents tested (amfonelic acid, benztropine, bupropion and mazindol) completely protected against DA depletion in the mouse striatum when given before DA-depleting doses of MPTP were administered, whereas atropine and trihexyphenidyl (which were employed for comparative purposes) did not. DA uptake blocking agents appear to represent a second general class of compounds, monoamine oxidase inhibitors being the first, which protect against the biologic effects of MPTP in the mouse.