The importance of the '4-5' double bond for neurotoxicity in primates of the pyridine derivative MPTP.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a newly recognized neurotoxin which selectively damages the cells of the substantia nigra in primates. It has been effective in producing an animal model for Parkinson's disease. We now report that saturating the '4-5' double bond in the tetrahydropyridine ring of MPTP prevents its metabolic oxidation to 1-methyl-4-phenylpyridinium ion (MPP+) and removes its behavioral and neurotoxic effects. We believe that this represents an important step towards elucidating the mechanism of action of this compound.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D010084:Oxidation-Reduction; D011725:Pyridines / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D011726:Pyridinium Compounds / Q000138:chemical synthesis / Q000633:toxicity*; D012453:Saimiri; D013329:Structure-Activity Relationship; D013378:Substantia Nigra / Q000187:drug effects
D011725:Pyridines; D011726:Pyridinium Compounds; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium