Abstract :
(−)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 than 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). Maintenance on (−)deprenyl prevents the characteristic age-related morphological changes in the neuromelanin granules of the neurocytes in the substantia nigra.
All in all, (−)deprenyl increases the activity of the nigrostriatal dopaminergic system and slows its age-related decline. Maintenance of male rats on (−)deprenyl delays the loss of the capacity to ejaculate, slows the decline of learning and memory, and significantly lengthens the lifespan as compared with saline-treated rats.
Parkinsonʹs disease patients on levodopa plus (−)deprenyl (10 mg daily) live significantly longer than those on levodopa alone. (−)Deprenyl is the first drug that retards the progress of Parkinsonʹs disease. Newly diagnosed Parkinsonʹs disease patients maintained on (−)deprenyl need levodopa significantly later than their placebo-treated peers. Maintenance on (−)deprenyl improves significantly the performance of patients with Alzheimerʹs disease. It is concluded that Parkinsonʹs disease and Alzheimerʹs disease patients need to be treated daily with 10 mg (−)deprenyl from diagnosis until death, irrespective of other medication.
We propose that the healthy population be maintained on 10–15 mg (−)deprenyl weekly starting at age 45 in order to combat the age-related decline of the nigrostriatal dopaminergic neurons. Prophylactic (−)deprenyl medication seems to offer a reasonable prospect of improving the quality of life in the later decades, delaying the time of natural death and decreasing the susceptibility of age-related neurological diseases, like Parkinsonʹs diesase and Alzheimerʹs disease.
