Neuroprotective and neuronal rescue effects of selegiline: review.

Abstract

The effect of selegiline [(-)-deprenyl] cannot be considered as a simple, selective inhibitor of MAO-B. Pretreatment with the drug prevented the effect of specific neurotoxins like MPTP, 6-OH-dopamine, DSP-4 and AF64A. Selegiline pretreatment prevented the depletion of noradrenaline (NA) induced by DSP-4 in the rat hippocampus. This can be due to the uptake inhibitory effect of selegiline and mainly to its metabolite methylamphetamine (MA), which is more potent inhibitor of the re-uptake than the parent compound. SKF-525A pretreatment diminished the protective effect of selegiline against DSP-4, while phenobarbital pretreatment decreased its MAO-B inhibitory potency. Selegiline in low oral doses also prevented the effect of DSP-4 due to its intensive "first pass" metabolism. Selegiline treatment can rescue damaged neurones. It inhibited the apoptosis in M-1 human melanoma cells in a rather low concentration (10(-13)M). The mode of action of the drug regarding the inhibition of apoptosis is not known.