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The
pharmacological basis of the beneficial effects of (-)deprenyl
(selegiline) in
Parkinson's and Alzheimer's diseases.
Knoll J
Department of Pharmacology,
Semmelweis University of Medicine, Budapest, Hungary.
J Neural Transm Suppl 1993;40:69-91
ABSTRACT
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.
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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