Deprenyl - effect of MAO-B inhibitors on MPP+ toxicity

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.
rmwu@ha.mc.ntu.edu.tw
Ann N Y Acad Sci 2000; 899:255-61

ABSTRACT

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.

Parkinson's research / abstracts

1.    Deprenyl effect on cognitive functions in early Parkinson's
2.    Deprenyl depression in Parkinson's disease
3.    Deprenyl stimulates biosynthesis of cytokines interleukin-1 & 6
4.    Deprenyl effect of MAO-B inhibitors on MPP+ toxicity
5.    Deprenyl modulates the decline of the dopamineric system
6.    Deprenyl possible mechanisms of action in Parkinson's
7.    Deprenyl pharmacological basis of the beneficial effects
8.    Deprenyl improves visuo-motor control in early Parkinsonism
9.    Deprenyl delays disability in Parkinsonian patients
10.   Deprenyl management of early Parkinson's disease
11.   Deprenyl delays the onset of disability in Parkinsonian patients
12.   Deprenyl and tocopherol antioxidative therapy of Parkinsonism