MPTP neurotoxicity: an overview and characterization of phases of toxicity

Abstract

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) produces unalloyed parkinsonism in humans when injected systemically, and has been effective in producing an animal model of Parkinson's disease in non-human primates. A distinction between toxic and pharmacologic effects of the compound is drawn, and basic criteria for animal models of human disease are reviewed, particularly as they relate to MPTP. A comparison between a unique population of humans affected by this substance and non-human primates is presented. The syndrome of MPTP intoxication can be divided into three and possibly four phases, and the potential underlying mechanisms for the clinical and behavior observations of each phase are discussed.