Paraquat and two endogenous analogues of the neurotoxic substance N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine do not damage dopaminergic nigrostriatal neurons in the mouse.
C57 black mice were injected repeatedly with maximal tolerated doses of 4 different chemical analogues of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), or its metabolite N-methyl-4-phenylpyridinium ion (MPP+), in order to assess their possible neurotoxicity for dopaminergic nigrostriatal neurons and their potential for causing idiopathic Parkinson's disease. The 4 analogues were the herbicide paraquat, reduced paraquat (having two N-methyl-tetrahydropyridine moieties), N-methyl-1,2,3,4-tetrahydroisoquinoline, and 2-methyl-1,2,3,4-tetrahydro-beta-carboline, the latter two compounds being possible endogenous neurotoxins. Contents of striatal dopamine, measured by high-performance liquid chromatography with electrochemical detection one month after injections were completed, were not depleted by any of these 4 compounds in mice. They might conceivably prove more neurotoxic in primates.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010269:Paraquat / Q000031:analogs & derivatives / Q000633:toxicity*; D011725:Pyridines / Q000378:metabolism / Q000633:toxicity*; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects*
D011725:Pyridines; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D010269:Paraquat; D004298:Dopamine