Pharmacological actions of l-deprenyl (selegiline) and other selective monoamine oxidase B inhibitors.
The acetylenic selective monoamine oxidase (MAO) type B suicide inhibitor, l-deprenyl (l-selegiline), has proved to be a useful adjuvant to L-dopa therapy and monotherapy of Parkinson's disease. Although not all features of its antiParkinson action are known, studies that used brains obtained at autopsy from patients who took l-deprenyl show that the selective inhibition of MAO-B with a concomitant increase of phenylethylamine and dopamine, but not of serotonin or noradrenaline, in the basal ganglia may be responsible for its mode of action. The increased life expectancy noted in patients with Parkinson's disease who received long-term therapy (9 years in an uncontrolled study) is another unexpected feature of the drug. These exciting data, if confirmed in other long-term clinical trials, may herald a neuroprotective approach to the treatment of this degenerative disease. More recent studies indicate that Parkinson's disease may eventually turn out to be a neurotoxic event resulting from oxidative stress-induced free radical species in the substantia nigra. Thus selective MAO-B inhibitors could represent a unique class of drugs, having symptomatic actions with possible neuroprotective and neurorescue actions in one.
Youdim
M B
MB
Department of Pharmacology, Technion-Bruce Rappaport Faculty of Medicine, Haifa, Israel.
Finberg
J P
JP
D000818:Animals; D006801:Humans; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy; D012642:Selegiline / Q000494:pharmacology*
D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline