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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
Author(s) -
D'Amato Robert J.,
Benham David F.,
Snyder Solomon H.
Publication year - 1987
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1987.tb04142.x
Subject(s) - neuromelanin , mptp , substantia nigra , neurotoxin , metabolite , chemistry , stereochemistry , biochemistry , dopamine , biology , neuroscience , dopaminergic
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.