(-)Deprenyl (selegiline), a catecholaminergic activity enhancer (CAE) substance acting in the brain

Research output: Contribution to journalArticle

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Abstract

β-Phenylethylamine and its long acting derivatives, the amphetamines, are mixed-acting stimulants of the sympathetic system in the brain. They enhance the impulse propagation mediated release of catecholamines (catecholaminergic activity enhancer effect) and displace catecholamines from their stores (catecholamine releasing effect). (-)Deprenyl (selegiline), a close structural relative to (-)methamphetamine, is the first catecholaminergic activity enhancer substance in clinical use devoid of catecholamine releasing property, being therefore free of the 'cheese effect' and of the dependence capacity of the amphetamines. (-)Deprenyl is also a highly potent and selective, irreversible inhibitor of monoamine oxidase type B. (-)Deprenyl enhances superoxide dismutase and catalase activity in the striatum, protects the nigrostriatal dopaminergic neurons against selective neurotoxins (6-hydroxy-dopamine MPTP, 4-N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) and prevents characteristic age-related morphological changes in the neurocytes of the substantia nigra. Maintenance of rats on (-)deprenyl during the postdevelopmental phase of their life slows the age-related decline of sexual and learning performances and prolongs life significantly. Patients with early, untreated Parkinson's disease maintained on (-)deprenyl need levodopa significantly later than their placebo-treated peers, and when on levodopa plus (-)deprenyl, they live significantly longer than patients on levodopa alone. In patients with moderately severe impairment from Alzheimer's disease, treatment with (-)deprenyl slows the progression of the disease. It may be supposed that a prophylactic low dose administration of a safe catecholaminergic activity enhancer substance during the postdevelopmental phase of life will slow the age-related decline of behavioral performances, delay natural death and decrease susceptibility to Parkinson's disease and Alzheimer's disease.

Original languageEnglish
Pages (from-to)57-66
Number of pages10
JournalPharmacology and Toxicology
Volume82
Issue number2
Publication statusPublished - 1998

Fingerprint

Selegiline
Brain
Catecholamines
Levodopa
Amphetamines
Parkinson Disease
Alzheimer Disease
Amphetamine-Related Disorders
Phenethylamines
Cheeses
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Monoamine Oxidase Inhibitors
Methamphetamine
Dopaminergic Neurons
Monoamine Oxidase
Neurotoxins
Cheese
Substantia Nigra
Catalase
Neurons

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

(-)Deprenyl (selegiline), a catecholaminergic activity enhancer (CAE) substance acting in the brain. / Knoll, J.

In: Pharmacology and Toxicology, Vol. 82, No. 2, 1998, p. 57-66.

Research output: Contribution to journalArticle

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