L-deprenyl prevents the cell hypoxia induced by dopaminergic neurotoxins, MPP+ and β-carbolinium:: a microdialysis study in rats

N-Methyl-4-phenylpyridinium (MPP+) and 2,9-di-methyl-norharmanium (2,9-Me2NH+), which is a beta -carbolinium proposed as an endogenous MPP+-like toxin underlying Parkinson's disease, are strong mitochondrial toxins. We have measured the extracellular lactate levels as a marker for the in vivo cell hypoxia in the striatum of freely moving rats. The perfusions with MPP+ and 2,9-Me2NH+ increased extracellular lactate levels in a dose-dependent manner. These increases in lactate levels were significantly prevented by the co-perfusion with 10 muM L-deprenyl, a selective monoamine oxidase (MAO)-B inhibitor, but not by pargyline, a non-specific MAO inhibitor. The increase in extracellular lactate levels was considered to be the reflection of the cell damage resulted from the impairment of mitochondrial function. The present results suggested that L-deprenyl would rescue nerve cells from these toxins through the direct influence on the mitochondrial electron transport. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.