Neuroprotective and neuronal rescue effects of selegiline: review.
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.
Magyar
K
K
Department of Pharmacodynamics, Semmelweis University of Medicine, Budapest, Hungary.
Haberle
D
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006801:Humans; D008996:Monoamine Oxidase Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009498:Neurotoxins / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D012642:Selegiline / Q000493:pharmacokinetics* / Q000627:therapeutic use
D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D009498:Neurotoxins; D012642:Selegiline