Abstract
After the L-dopa revolution in the treatment of Parkinson’s disease (for review, see ref.1), there was a decade of consolidation, characterized by small but important variations on this therapeutic theme. However, in 1979, another great leap forward occurred when Davis et al. (2) clearly delineated the beginnings of the MPTP story. The sequence of events is now well known. Following that original publication, there was little interest until the phenomenon was rediscovered by Langston and his colleagues (3) in 1983, and the whole thing caught fire. Thus, a prodrug, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), had been discovered and shown to be neurotoxic only when converted by monoamine oxidase (MAO) B (4) to its quaternary ammonium derivative, 1-methyl-4-phenylpyridinium (MPP+). Administration of MPTP to man (2,3), or monkey (5) but not to rat (6) results in the best simulation of idiopathic Parkinson’s disease that we possess, which responds characteristically to L-dopa (5). The MPTP-treated monkey fails to develop the characteristic nigrostriatal lesions if pretreated with an MAO B inhibitor (7,8), a major signpost for what was to follow.
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Sandler, M., Glover, V. (1990). Biochemical Studies on Predisposition to Parkinson’s Disease. In: Nagatsu, T., Fisher, A., Yoshida, M. (eds) Basic, Clinical, and Therapeutic Aspects of Alzheimer’s and Parkinson’s Diseases. Advances in Behavioral Biology, vol 38A. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5844-2_46
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