Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6 -tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity.

摘要: N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces neuropathological and clinical abnormalities in humans, monkeys, mice that closely resemble idiopathic parkinsonism. N-Methyl-4-phenylpyridine (MPP+), a metabolite of MPTP formed by monoamine oxidase B, is accumulated into striatal cerebral cortical synaptosomes the dopamine norepinephrine uptake systems, respectively, whereas itself not accumulated. The potencies drugs inhibiting [3H]MPP+ or [3H]dopamine are very similar, as [3H]norepinephrine synaptosomes. Km values for 170 65 nM Vmax 2 0.1 nmol/g tissue per min rat striatum cortex, similar to uptake, Autoradiography slices brain shows high densities caudate-putamen nucleus accumbens. Furthermore, blockade mazindol prevents MPTP-induced damage nigrostriatal neurons, indicating MPP+ concentration neurons explains their selective destruction MPTP.