Characterization of the Binding of N-Methyl-4-Phenylpyridine, the Toxic Metabolite of the Parkinsonian Neurotoxin N-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine, to Neuromelanin |
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Authors: | Robert J D'Amato David F Benham Solomon H Snyder |
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Institution: | Departments of Neuroscience, Pharmacology and Experimental Therapeutics, Psychiatry, and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A. |
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Abstract: | N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) selectively destroys neuronal cell bodies in the neuromelanin-containing substantia nigra of humans and primates. We show that N-methyl-4-phenylpyridine (MPP+), the active metabolite of MPTP, binds to neuromelanin with high affinity. This binding increases at higher pH and is displaced most potently by divalent cations and antimalarial drugs. MPP+ bound intracellularly to neuromelanin may be stored and released gradually, resulting in subsequent damage to neurons of the substantia nigra. |
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Keywords: | N-Methyl- 4 - phenyl -1 2 3 6 - tetrahydropyridine N- Methyl-4-phenylpyridine Neuromelanin Parkinson's disease Neurotoxicity |
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