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

Robert J. D'Amato, David F. Benham, Solomon H. Snyder

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)653-658
Number of pages6
JournalJournal of Neurochemistry
Volume48
Issue number2
DOIs
StatePublished - Feb 1987

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Keywords

  • Neuromelanin
  • Neurotoxicity
  • N‐ Methyl‐4‐phenylpyridine
  • N‐Methyl‐ 4 ‐ phenyl ‐1,2,3,6 ‐ tetrahydropyridine
  • Parkinson's disease

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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