Effect of MAO-B inhibitors on MPP+ toxicity in Vivo.
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.
Wu
R M
RM
Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. rmwu@ha.mc.ntu.edu.tw
Chen
R C
RC
Chiueh
C C
CC
D015655:1-Methyl-4-phenylpyridinium / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D008297:Male; D008995:Monoamine Oxidase / Q000187:drug effects; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology
D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D012642:Selegiline; D008995:Monoamine Oxidase; D015655:1-Methyl-4-phenylpyridinium