MPTP and Monoamine Oxidase B Inhibitors

Abstract

Parkinson's disease is caused by the imbalance of dopaminergic and cholinergic neurotransmittersParkinson's disease is caused by the imbalance of dopaminergic and cholinergic neurotransmittersin the central nervous system. Damages of substantia nigra, by endogenous (e.g., formations of oxygen freeradical and hydrogen peroxide) and exogenous (e.g., viral infection and environmental toxins) factors,decrease dopamine level resulting in Parkinsonism syndrome. N-Methyl-4-phenyl-tetrahydropyridine (MPTP),an exogenous cause of the disease, is metabolized by monoamine oxidase B (MAO B) to the toxic species,MPP. . Design of mechanism-based MAO B inhibitors provides a novel protection pathway against thisneurotoxin. Five major classes of MAO B inhibitors are described in this paper: acetylenic, arylhydrazine,benzyl-dimethyl-silyl-methanamine, (aminoalkyl)trimethylsilanes and novel MPTP analogs including1-substituted-4-phenyl-tetrahydropyridine and 1-methyl-4-substituted-tetrahydropuridine derivatives.