Rationale for (-)deprenyl (selegiline) medication in Parkinson's disease and in prevention of age-related nigral changes.
(-)Deprenyl (selegiline, jumex, eldepryl, movergan), a close structural relative 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), a predominantly glial enzyme in the brain. The activity of this enzyme significantly increases with age. (-)deprenyl, the first selective inhibitor of MAO-B described in literature, has become the universally used research tool for selectively blocking B-type MAO. It is the only selective MAO-B inhibitor in clinical use. (-)Deprenyl interferes with the uptake of catecholamines and indirectly acting sympathomimetics because it is handled by the catecholaminergic neuron in a way similar to the physiological substances transported through the axonal end organ and vesicular membrane. The unique behavior of (-)deprenyl is that, in striking contrast to PEA and its relatives it does not displace the transmitter from storage, ie it is not a releaser. The net result is that (-)deprenyl inhibits the releasing effect of tyramine, and at present, is the only safe MAO inhibitor that can be administered without dietary precautions. Maintenance on (-)deprenyl selectively enhances superoxide dismutase (SOD) and catalase activity in the striatum. This effect is unrelated to its effect on MAO-B and the inhibitory effects of the drug on neurotransmitter uptake. Maintenance on (-)deprenyl facilitates the activity of the catecholaminergic system in the brain, and this effect, too, is unrelated to either its effects on MAO or on neurotransmitter uptake. (-)Deprenyl protects the nigrostriatal dopaminergic neurons against selective neurotoxins (6-hydroxydopamine, MPTP, DSP-4).(ABSTRACT TRUNCATED AT 250 WORDS)
Knoll
J
J
Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary.
D000375:Aging; D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D004334:Drug Administration Schedule; D006801:Humans; D010300:Parkinson Disease / Q000188:drug therapy*; D012642:Selegiline / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*
D000978:Antiparkinson Agents; D012642:Selegiline