Rationale for deprenyl (selegiline) medication in Parkinson's disease and in prevention of age-related nigral changes.

Knoll J.

Department of Pharmacology, 
Semmelweis University of Medicine, Budapest, Hungary.
Biomed Pharmacother 1995;49(4):187-95

Abstract

Deprenyl (selegiline, jumex, eldepryl, movergan), a close structural relative 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), 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 literature, has become the universally used research tool for selectively blocking B-type MAO. It is the only selective MAO-B inhibitor in clinical use. (-)Deprenyl interferes with the uptake of catecholamines and indirectly acting sympathomimetics because it is handled by the catecholaminergic neuron in a way similar to the physiological substances transported through the axonal end organ and vesicular membrane. The unique behavior of (-)deprenyl is that, in striking contrast to PEA and its relatives it does not displace the transmitter from storage, ie it is not a releaser. The net result is that (-)deprenyl inhibits the releasing effect of tyramine, and at present, is the only safe MAO inhibitor that can be administered without dietary precautions. Maintenance on (-)deprenyl selectively enhances superoxide dismutase (SOD) and catalase activity in the striatum. This effect is unrelated to its effect on MAO-B and the inhibitory effects of the drug on neurotransmitter uptake. Maintenance on (-)deprenyl facilitates the activity of the catecholaminergic system in the brain, and this effect, too, is unrelated to either its effects on MAO or on neurotransmitter uptake. (-)Deprenyl protects the nigrostriatal dopaminergic neurons against selective neurotoxins (6-hydroxydopamine, MPTP, DSP-4).

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