|
| |
|
Deprenyl (selegiline), a catecholaminergic
activity enhancer (CAE) substance acting in the brain
Knoll J
Department of Pharmacology,
Semmelweis University of Medicine,
Budapest, Hungary.
Pharmacol Toxicol 1998 Feb; 82(2):57-66
ABSTRACT
beta-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.
|
-
-
|