Anti-apoptotic and apoptotic action of (-)-deprenyl and its metabolites.

The mode of cytoprotective action of the monoamine oxydase B inhibitor (-)-deprenyl was studied using A-2058 human melanoma cells in culture. Serum deprivation caused apoptosis of the cultured cells, which could be decreased by administration of 10(-9) - 10(-13)M (-)-deprenyl. The known metabolites of (-)-deprenyl, (-)-desmethyl-deprenyl, (-)- and (+)-methylamphetamine failed to exert the same effect. The anti-apoptotic activity of (-)-deprenyl was prevented by the simultaneous application of the microsomal drug-metabolizing enzyme inhibitor SKF-525A. These results show that (-)-deprenyl needs metabolic conversion in order to be anti-apoptotic, but the effective metabolite is still unknown. On the other hand, higher dose (10(-13)M) of (-)-deprenyl, (-)-desmethyl-deprenyl, (-)- and (+)-methylamphetamine induced apoptosis in the non-serum-deprived A-2058 cell culture. SKF-525A did not prevent the apoptosis-inducing effect of (-)-deprenyl, which means that no metabolic changes are needed for this activity. High dose (10(-3)M) of (-)-deprenyl induced very high Caspase 3 activity in non-serum-deprived A-2058 cell culture, low doses (10(-9) - 10(-3) M) of (-)-deprenyl maintained Caspase 3 activity on control level in case of serum-deprivation.