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Rationale for deprenyl (selegiline)
medication in Parkinson's disease and in prevention of age-related nigral
changes.
Knoll J.
Department of Pharmacology,
Semmelweis University of Medicine, Budapest, Hungary.
Biomed Pharmacother 1995;49(4):187-95
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 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).
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Parkinson's
research / abstracts
1.
Deprenyl
effect on cognitive functions in early Parkinson's
2. Deprenyl
depression in Parkinson's disease
3. Deprenyl
stimulates biosynthesis of cytokines interleukin-1 & 6
4. Deprenyl
effect of MAO-B inhibitors on MPP+ toxicity
5. Deprenyl
modulates the decline of the dopamineric system
6. Deprenyl
possible
mechanisms of action in Parkinson's
7. Deprenyl
pharmacological
basis of the beneficial effects
8. Deprenyl
improves visuo-motor
control in early Parkinsonism
9. Deprenyl
delays
disability in Parkinsonian patients
10. Deprenyl
management of
early Parkinson's disease
11. Deprenyl
delays the
onset of disability in Parkinsonian patients
12. Deprenyl
and tocopherol
antioxidative therapy of Parkinsonism
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