(-)Deprenyl (Selegiline, Jumex, Eldepryl,
Movergan), a close structural relative to phenylethylamine (PEA), is a drug
with a unique pharmacological spectrum.
(1) 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 MAO-B inhibitor in clinical
2) (-)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.
(3) 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.
(4) Maintenance on (-)deprenyl facilitates
the activity of the nigrostriatal dopaminergic neurons with remarkable
selectivity, and this effect, too, is unrelated to either its effects on MAO
or on neurotransmitter uptake.
(5) 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 life-span as compared with saline-treated
rats. Parkinson's 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 Parkinson's disease.
Newly diagnosed Parkinson's disease patients maintained on (-)deprenyl need
levodopa significantly later than their placebo-treated peers.
Maintenance on (-)deprenyl improves significantly the performance of
patients with Alzheimer's disease. It is concluded that Parkinson's
disease and Alzheimer's disease patients need to be treated daily with 10 mg
(-)deprenyl from diagnosis until death, irrespective of other medication.