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  • Title: The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on presynaptic dopamine uptake sites in the mouse striatum.
    Author: Donnan GA, Kaczmarczyk SJ, Rowe PJ, Figdor R, Mendelsohn FA.
    Journal: J Neurol Sci; 1986 Jun; 74(1):111-9. PubMed ID: 3487620.
    Abstract:
    The effects of the specific dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), were studied on the kinetics of [3H]mazindol binding to striatal membranes of C57 black mice. This radioligand was used to label dopamine uptake sites and when administered in vivo, MPTP caused an irreversible, non-competitive inhibition of mazindol binding, consistent with damage to dopaminergic terminals. This effect was abolished by pretreatment with pargyline, a MAOB inhibitor, suggesting that oxidation of MPTP to the pyridinium moiety, MPP+, is a necessary step for toxicity when mazindol binding is used as an end point. In keeping with these findings, pretreatment of mice with mazindol protected against the dopamine-depleting effects of MPTP in vivo. This data suggests that MPTP exerts its toxic effects via MPP+ which is concentrated intraneuronally via the dopamine uptake system. During this process the neurotoxin irreversibly inactivates the dopamine uptake sites.
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