Role of Active Oxygen in Paraquat and 1-Methyl-4-phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Cytotoxicity
The cyclic tertiary amine l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) is a contaminant of the illicitly synthesized meperidine analog MPPP and is able to induce symptoms which closely resemble idiopathic Parkinsons disease (PD) in humans.1 This appears to be caused by a selective destruction of dopaminergic neurons in the zona compacta of the substantia nigra, as seen following the administration of MPTP to primates.2 Metabolic activation of the compound seems to be essential for its cytotoxic action.3 Mitochondrial monoamine oxidase type B converts MPTP to MPDP+, which is further oxidized to MPP+, the ultimate toxic metabolite.4
KeywordsGlutathione Reductase Dopaminergic Neuron Redox Cycling Zona Compacta Selective Destruction
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- 2.R. S. Burns, C. C. Chiueh, S. P. Markey, M. H. Ebert, D. M. Jacobowitz, and I. J. Kopin, A primate model of parkinsonism: Selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Proc. Natl. Acad. Sci. USA 80:4545 (1983).Google Scholar
- 5.A. Barbeau, M. Roy, T. Cloutier, L. Piasse, and S. Paris, Environmental and genetic factors in the etiology of Parkinson’s disease, in “Advances in Neurology,” vol. 45, M. D. Yahr and K. J. Bergman, eds., Raven Press, New York (1986).Google Scholar
- 16.G. Ekstrom, D. Di Monte, M. S. Sandy, and M. T. Smith, Comparative toxicity and antioxidant activity of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine and its monoamine oxidase B-generated metabolites in isolated hepatocytes and liver microsomes, Arch. Biochem. Biophys. 255:14 (1987).PubMedCrossRefGoogle Scholar