Mptp-Induced Parkinsonism. [Review]

Stern, Yaakov

In 1979, the publication of a little noticed article presaged a major advance in the knowledge of and research approaches to Parkinson's disease (PD) (Davis et al., 1979). The paper reported the case history of a 23-year-old man who, in 1973, developed parkinsonian symptoms including bradykinesia, rigidity and tremor which progressed to mutism and virtual paralysis over a period of days. His physicians determined that he had been preparing and self-injecting a potent meperedine analogue 1-methyl-4- phenyl-propionoxypiperidine (MPPP), apparently as a substitute for demerol. He had taken some short cuts in the preparation of the compound, resulting in the presence of a by-product, 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP), which was apparently responsible for the parkinsonian syndrome. The patient responded to the standard dopamine replacement therapy used in PD. Following his untimely death, post-mortem examination revealed depletion of cells in the pars compacta of the substantia nigra, the characteristic pathologic change of PD. These observations suggested for the first time that exposure to a toxin might produce a disease that has no known cause.


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Progress in Neurobiology

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February 23, 2018