THE PHARMACOLOGY OF B-TYPE SELECTIVE MONOAMINE-OXIDASE INHIBITORS - MILESTONES IN (-)-DEPRENYL RESEARCH

(-)-deprenyl cannot be considered as a simple, selective inhibitor of MAO-B. It increases the dopaminergic tone in the central nervous syste m by a complex mechanism. The MAO-B inhibition could result in a poten tiation of the effect and the reduction of the dose of L-dopa, includi ng the restoration of the sensitivity to L-dopa treatment, when the re sponse to the drug has already been diminished or lost. Pre-treatment with (-)deprenyl prevent the effect of neurotoxins like MPTP, 6-hydrox ydopamine, DSP-LC, AF64A by inhibiting the conversion of the pretoxin to toxin, or by inhibiting the neuronal reuptake mechanisms, or the co mbination of the two processes. However, other effects of the inhibito r cannot be ruled out. (-)deprenyl, but not its (+)-enantiomer, proved to be a potent inhibitor of programmed cell death (apoptosis) of PC12 cells and that of human melanoma cells, in a concentration which does not induce MAO-B inhibition. The activity of MAO-B increases with age and the age related changes led to an overproduction of neurotoxic ag ents. The inhibition of the enzyme activity can play a preventive role against neurodegenerative brain disorders. The most widely used MAO-B inhibitor in the therapy is (-)-deprenyl and it lacks the ''cheese re action''. The complex mechanism for the lack of the former effect is n ot fully known.