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

R. J. D'Amato, D. F. Benham, Solomon H Snyder

Research output: Contribution to journalArticle

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
StatePublished - 1987

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1-Methyl-4-phenylpyridinium
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Poisons
Neurotoxins
Metabolites
Substantia Nigra
Divalent Cations
Antimalarials
Primates
Neurons
Cells
neuromelanin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

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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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year = "1987",
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T1 - 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

AU - D'Amato, R. J.

AU - Benham, D. F.

AU - Snyder, Solomon H

PY - 1987

Y1 - 1987

N2 - 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.

AB - 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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