The pharmacological basis of the beneficial effects of (-)deprenyl (selegiline) in Parkinson's and Alzheimer's diseases.
(-)Deprenyl (Selegiline, Jumex, Eldepryl, Movergan), structurally closely related to phenylethylamine (PEA), is a drug with a unique pharmacological spectrum. It is a highly potent and selective irreversible inhibitor of B-type monoamine oxidase (MAO) and interferes with the uptake of catecholamines and indirectly acting symphathomimetics. In striking contrast to PEA and its relatives, which displace the transmitter from the storage places, (-)deprenyl inhibits the releasing effect of tyramine and is up to the present the only safe MAO inhibitor which can be administered without dietary restrictions. Maintenance on (-)deprenyl enhances selectively superoxide dismutase (SOD) and catalase activities in the striatum. This effect is unrelated to the MAO and uptake inhibitory effects of the drug. Maintenance on (-)deprenyl facilitates the activity of the nigrostriatal dopaminergic neurons with remarkable selectivity and this effect too, is unrelated to either the MAO or the uptake inhibitory effects of the drug. Maintenance on (-)deprenyl prevents the characteristic age-related morphological changes in the neuromelanin granules of the neurocytes in the substantia nigra. As a consequence of its complex spectrum of activity male rats maintained on (-)deprenyl live longer, lose their capacity to ejaculate later, show improved performance in learning tests and maintain this activity for a longer period than their untreated peers. Patients with Parkinson's disease maintained on levodopa plus (-)deprenyl (10 mg daily) live significantly longer than those on levodopa alone. Freshly diagnosed patients treated with (-)deprenyl need levodopa later than their placebo-treated peers. Continuous administration of (-)deprenyl improves the performance of patients with Alzheimer's disease.
Knoll
J
J
Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary.
D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology*; D004359:Drug Therapy, Combination; D007858:Learning / Q000187:drug effects; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D012642:Selegiline / Q000627:therapeutic use*; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D012642:Selegiline; D007980:Levodopa; D002374:Catalase; D013482:Superoxide Dismutase