Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: Characterization and localization of receptor binding sites in rat and human brain

J. A. Javitch, G. R. Uhl, S. H. Snyder

Research output: Contribution to journalArticlepeer-review

Abstract

N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces neuropathologic and clinical abnormalities in humans and animals that closely resemble idiopathic Parkinson disease. [3H]MPTP binds with high affinity (K(d) = 28 x 10-9 M) to brain membranes. The chemical specificity of the binding sites corresponds to structure-activity requirements for neurotoxicity. Autoradiographic studies in human brain show very high receptor densities in the caudate, substantia nigra, and locus coeruleus, which may explain the neurotoxic and neurochemical sequelae of MPTP administration. In contrast to the human, rat substantia nigra and caudate display only moderate receptor concentrations. This species difference may explain the difficulty in producing selective nigrostriatal degeneration in rats. Sites densely labeled in rat brain include the locus ceruleus, interpeduncular nucleus, arcuate and periventricular hypothalamic nuclei, and the subfornical organ.

Original languageEnglish (US)
Pages (from-to)4591-4595
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume81
Issue number14 I
DOIs
StatePublished - 1984

ASJC Scopus subject areas

  • General

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