Effect of MAO-B inhibitors
on MPP+ toxicity in Vivo
Wu RM, Chen RC, Chiueh CC
Department of Neurology,
National Taiwan University Hospital,
College of Medicine,
National Taiwan University, Taipei, Taiwan.
Ann N Y Acad Sci 2000; 899:255-61
l-Deprenyl (Selegiline), a selective and irreversible type B monoamine oxidase inhibitor, has been used as an adjunct to levodopa therapy in Parkinson's disease. Recently, it is proposed as a putative neuroprotective agent in delaying the progression of cell death based on its capability of reducing the oxidative stress derived from the MAO-B dependent metabolism of dopamine, and blocking the development of MPTP-parkinsonism. However, a variety of experimental models suggest that l-deprenyl provides neuroprotection through multiple modes of mechanism other than the inhibition of MAO-B. We have previously shown that l-deprenyl protects midbrain dopamine neurons from MPP+ toxicity by a novel antioxidant effect.
In the present study we examined whether the protection against MPP+ toxicity is also shared by other reversible or irreversible MAO-B inhibitors including (+)-deprenyl, Ro16-6491 and pargyline. Our data show that non of these MAO-B inhibitors changes the dopamine loss in the striatum induced by intranigral injection of MPP+.
Our result suggests that l-deprenyl may possess a unique neuroprotective action on nigral neuron against MPP+ toxicity independent of the MAO-B inhibition.