Mechanisms of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity to striatal dopamine neurons in mice.
MPTP given to mice in 4 daily doses (20 mg/kg s.c.) resulted in 56-70% depletion of striatal dopamine 1 week after the last dose. Pretreatment with deprenyl or MD 240928, selective inhibitors of monoamine oxidase type B, or with amfonelic acid or nomifensine, selective inhibitors of dopamine uptake, prevented the depletion of striatal dopamine. In contrast, pretreatment with alpha-methyl-tyrosine, Ro 4-1284 or haloperidol did not prevent the depletion of striatal dopamine by MPTP. The results are compatible with the view that dopamine itself is not involved in the neurotoxic effect of MPTP but that MPP+, a metabolite of MPTP formed by MAO-B and accumulated by the dopamine uptake carrier, is responsible for the neurotoxicity.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D051379:Mice; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000633:toxicity*
D011725:Pyridines; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine