Disposition of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice before and after monoamine oxidase and catecholamine reuptake inhibition.

The distribution of radioactivity in pigmented mice after a single intravenous injection of 1-(3H) methyl-4-phenyl-1,2,3,6-tetrahydropyridine (3H-MPTP) was studied by quantitative whole body autoradiography and liquid scintillation counting. Pretreatment with the monoamine oxidase inhibitors clorgyline, pargyline and deprenyl, or the catecholamine reuptake inhibitor nomifensine was performed 30 min. prior to the 3H-MPTP administration. A high uptake of radioactivity was observed in the striatum, nucleus accumbens, midbrain area and locus coeruleus, and also in the adrenal medulla. This uptake was inhibited by deprenyl or pargyline pretreatment, but not after clorgyline or nomifensine pretreatment. An extensive uptake which was not influenced by deprenyl or pargyline treatment was found in the melanin-containing tissues of the eye. This accumulation is due to the melanin affinity of MPTP and its metabolites. A comparatively rapid elimination from the brain of MPTP and its metabolites was observed, which may be due to the lack of neuromelanin in mice.