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The Neurotoxicity of 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine in the Monkey and Man

Published online by Cambridge University Press:  18 September 2015

R. Stanley Burns ,
Sanford P. Markey ,
Jere M. Phillips  and
Chuang C. Chiueh
Sanford P. Markey
Affiliation:
Section on Analytical Biochemistry, Laboratory of Clinical Sciences, National Institute of Mental Health, Bethesda, Maryland
Jere M. Phillips
Affiliation:
Section on Laboratory Animal Medicine and Care, National Institute of Mental Health, Bethesda, Maryland
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Abstract

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l-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) selectively destroys dopaminergic neurons in the pars compacta of the substantia nigra (A8 and A9 cells). MPTP or its metabolite enters nerve cells at the level of their terminals in the caudate nucleus and putamen leading to a disturbance in axoplasmic flow and retrograde degeneration. The species-dependent neurotoxicity of MPTP (primate vs. rodent) suggests that a biochemical property of the cell related to neuromelanin may be important in the mechanism of cell injury.

Type
4. Toxic Environmental Factors Causing Parkinsonism
Information
Canadian Journal of Neurological Sciences , Volume 11 , Issue S1: Current Concepts and Controversies in Parkinson’s Disease , February 1984 , pp. 166 - 168
Copyright
Copyright © Canadian Neurological Sciences Federation 1984

References

Ambani, LM, Van Woert, MH, Murphy, S (1975) Brain peroxidase and catalase in Parkinson disease. Arch. Neurol. 32: 114–118.CrossRefGoogle ScholarPubMed
Barden, H (1981) The biology and chemistry of neuromelanin. In Age Pigments, Sohal, RS (Ed), 155–180, Elsevier/North-Holland Biomedical Press, Amsterdam.Google Scholar
Barden, H, Levine, S (1983) Histochemical observations on rodent brain melanin. Brain Res. Bull. 10: 847–851.CrossRefGoogle ScholarPubMed
Burns, RS, Chiueh, CC, Markey, SP, Ebert, MH, Jacobowitz, DM, Kopin, IJ (1983) A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-l, 2, 3, 6-tetrahydropyridine. Proc. Natl. Acad. Sci. USA, 80: 4546–4550.CrossRefGoogle Scholar
Chandra, SV, Srivastava, RS, Shukla, GS (1979) Regional distribution of metals and biogenic amines in the brain of monkeys exposed to manganese. Toxicology Lett. 4: 189–192.CrossRefGoogle Scholar
Chiueh, CC, Markey, SP, Burns, RS, Johannessen, JN, Pert, A, Kopin, IJ (1984) Neurochemical and behavioral effects of systemic and intranigral administration of N-methyl-4-phenyl-l, 2, 3, 6-tetrahydropyridine in the rat. Eur. J. Pharmacol. (Accepted).CrossRefGoogle Scholar
Davis, GC, Williams, AC, Markey, SP, Ebert, MH, Caine, ED, Reichert, CM, Kopin, IJ (1979) Chronic parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatry Res. I: 249–254.CrossRefGoogle Scholar
Donaldson, J, McGregor, D, Labella, F (1982) Manganese neurotoxicity: a model for free radical mediated neurodegeneration? Can. J. Physiol. Pharmacol. 60: 1393–1405.CrossRefGoogle Scholar
Graham, DG (1978) Oxidatiue pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol. Pharmacol. 14:633–643.Google ScholarPubMed
Graham, DG, Tiffany, SM.Bell, WR, Gutknecht, (1978) Autoxidation verses covalent binding of quinones as the mechanism of toxicity of dopamine, 6-hydroxdopamine, and related compounds toward C 1300 neuroblastoma cells in vitro. Mol. Pharmacol. 14: 644–653.Google Scholar
Gupta, SK, Murthy, RC, Chandra, SV (1980) Neuromelanin in manganese-exposed primates. Toxicology Lett. 6: 17–20.CrossRefGoogle ScholarPubMed
Klawans, HL, Stein, RW, Tanner, CM, Goetz, CG (1982) A pure parkinsonian syndrome following acute carbon monoxide intoxication. Arch Neurol. 39: 302–304.CrossRefGoogle ScholarPubMed
Langston, JW, Ballard, P, Tetrud, JW, Irwin, I (1983) Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science. 219: 979–980.CrossRefGoogle ScholarPubMed
Ledig, M, Fried, R, Ziessel, M, Mandel, P (1982) Regional distribution of superoxide dismutase in rat brain during postnatal development. Developmental Brain Research. 4: 333–337.CrossRefGoogle Scholar
Neff, NH, Barrett, RE, Costa, E (1969) Selective depletion of caudate nucleus dopamine and serotonin during chronic manganese dioxide administration to squirrel monkeys. Experientia. 25: 1140–1141.CrossRefGoogle ScholarPubMed
Richter, R (1945) Degeneration of the basal ganglia in monkeys from chronic carbon disulfide poisoning. J. Neuropath. Exp. Neurol. 4: 324–353.CrossRefGoogle ScholarPubMed
Sachs, C, Jonsson, G (1975) Mechanisms of action of 6-hydroxydopamine. Biochem. Pharmacol. 24: 1–8.CrossRefGoogle ScholarPubMed