Voprosy meditsinskoi khimii (ISSN 0042-8809)

The history of (-)deprenyl the first selective inhibitor of type b monoamine oxidase

   
Knoll J.
PubMed Id: 9503565
Year: 1997 vol: 43  issue:6  pages: 482-493
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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Reference: Knoll J., The history of (-)deprenyl the first selective inhibitor of type b monoamine oxidase, Voprosy meditsinskoi khimii, 1997, vol: 43(6), 482-493.
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