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The importance of the ‘4–5’ double bond for neurotoxicity in primates of the pyridine derivative MPTP |
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| Authors: | J.William Langston Ian Irwin Elizabeth B. Langston Lysia S. Forno |
| Affiliation: | 1 Department of Neurology, Santa Clara Valley Medical Center, San Jose, CA 95128, U.S.A. 2 Department of Pathology, Veterans Administration Medical Center, Palo Alto, CA 94304, U.S.A. 3 Stanford University School of Medicine, Stanford, CA 94305, U.S.A. |
| Abstract: | 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. |
| Keywords: | 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine MPTP substantia nigra neurotoxicity Parkinson's disease animal model 1-methyl-4-phenylpiperidine MPP |
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