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History
of deprenyl
the first selective inhibitor of monoamine oxidase type B
Knoll J
Department of Pharmacology
Semmelweis University of Medicine
Budapest, Hungary.
Vopr Med Khim,
1997 Nov, 436, 482-93
ABSTRACT
(-)Deprenyl (Selegiline, Jumex,
Eldepryl, Movergan), a close structural relative of
phenylethylamine (PEA), is a drug with a unique pharmacological
spectrum. Whereas PEA and its long-lasting variants, the
amphetamines, are mixed-acting stimulants of the sympathetic
system in the brain, they primarily enhance the impulse
propagation generated release of catecholamines (catecholamine
activity enhancer, CAE, effect) and displace catecholamines in
higher concentration (catecholamine releasing effect). (-)Deprenyl
is the first CAE substance in clinical use devoid of catecholamine
releasing activity. (-)Deprenyl 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 the literature, has
become a universally used research tool for selectively blocking
B-type MAO and is still the only selective MAO-B inhibitor in
world wide clinical use. In contrast to MAO inhibitors which
strongly potentiate the catecholamine releasing effect of tyramine,
(-)deprenyl inhibits it and is free of the 'cheese effect', which
makes it a safe drug. Because its lack of the catecholamine
releasing activity (-)deprenyl is devoid of amphetamine like
dependence capacity. Maintenance on (-)deprenyl selectively
enhances superoxide dismutase (SOD) and catalase activity in the
striatum and protects the nigrostriatal dopaminergic neurons from
selective neurotoxins (6-hydroxydopamine, MPTP, DSP-4).
Maintenance of an animal on (-)deprenyl prevents the
characteristic age-related morphological changes in the
neuromelanin granules of the neurocytes in the substantia nigra.
Many other protective effects of (-)deprenyl, denoted as 'neuroprotective',
'trophiclike neurorescue', 'apoptosis reducing', etc, have been
described. All the protective actions of (-)deprenyl are thought
to be primarily related to the CAE effect of the drug. 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 age-related loss of their
capacity to ejaculate, slows the age-related decline of their
learning capacity and prolongs their life. Parkinsonian patients
on levodopa plus (-)deprenyl (10 mg daily) live significantly
longer than those on levodopa alone. Parkinsonian patients
maintained, after diagnosis, on (-)deprenyl, need levodopa
significantly later than their placebo-treated peers. Maintenance
on (-)deprenyl significantly improves the performance of patients
with Alzheimer's disease. It is concluded that patients developing
Parkinson's or Alzheimer's disease need to be treated daily with
10 mg (-)deprenyl from diagnosis until death, irrespective of
other medication. Because of the peculiar pharmacological spectrum
and safety of the drug it may be advisable to combat the
age-related decline of the nigrostriatal dopaminergic neurons in
man by taking 10-15 mg (-)deprenyl weekly during the
postdevelopmental phase of life. Prophylactic (-)deprenyl
medication may improve the quality of life in the latter decades,
delaying the time of natural death and decreasing the
susceptibility to age-related neurological diseases.
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