Does 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) cause Parkinson disease (PD)?

Updated: Aug 29, 2019
  • Author: Robert A Hauser, MD, MBA; Chief Editor: Selim R Benbadis, MD  more...
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Answer

Several individuals were identified who developed parkinsonism after self-injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). These patients developed bradykinesia, rigidity, and tremor, which progressed over several weeks and improved with dopamine replacement therapy. MPTP crosses the blood-brain barrier and is oxidized to 1-methyl-4-phenylpyridinium (MPP+) by monoamine oxidase (MAO)-B. [6]

MPP+ accumulates in mitochondria and interferes with the function of complex I of the respiratory chain. A chemical resemblance between MPTP and some herbicides and pesticides suggested that an MPTP-like environmental toxin might be a cause of Parkinson disease, but no specific agent has been identified. Nonetheless, mitochondrial complex I activity is reduced in Parkinson disease, suggesting a common pathway with MPTP-induced parkinsonism.


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