Monoamine Oxidase Inhibitors in Toxic Models of Parkinsonism

Monoamine oxidase inhibitors are widely used for the symptomatic treatment of Parkinson's disease (PD). They demonstrate antiparkinsonian activity in different toxin-based models induced by 6-hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and pesticides (rotenone and paraquat). In some models, such as MPTP-induced PD, MAO inhibitors prevent the formation of the neurotoxin MPP⁺ from the protoxin MPTP. Regardless of the toxin's nature, potent MAO inhibitors prevent dopamine loss reduction, the formation of hydrogen peroxide, hydrogen peroxide signaling, and the accumulation of hydrogen peroxide-derived reactive oxygen species responsible for the development of oxidative stress. It becomes increasingly clear that some metabolites of MAO inhibitors (e.g., the rasagiline metabolite 1-R-aminoindan) possess their own bio-pharmacological activities unrelated to the parent compound. In addition, various MAO inhibitors exhibit multitarget action, in which MAO-independent effects prevail. This opens new prospects in the development of novel therapeutics based on simultaneous actions on several prospective targets for the therapy of PD.