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The possible mechanisms of action of (-)deprenyl in Parkinson's disease

J Knoll

J Neural Transmission (AUSTRIA), 1978, 43/3-4 (177-198)

ABSTRACT

Deprenyl, a selective inhibitor of MAO-B, was found to be 60 times less potent in inhibiting intestinal MAO in the rat than clorgyline, the selective inhibitor of MAO-A.  This is one of the reasons why (-)deprenyl is safe with respect to the hazards involved in combination with a variety of foods and drugs and its administration is not contraindicated in parkinsonian patients. (-)Deprenyl is a potent inhibitor of the uptake of amines into the nerve endings of catecholaminergic neurons. With the aid of N-methyl-N-propargyl-/1-indenyl/-ammonium. HC1 (J-508), a newly developed highly potent MAO inhibitor, devoid of uptake-inhibitory and releasing effects, a tyramine-uptake model for testing the effects of MAO inhibitors on uptake, using different isolated noradrenergic organs (cat nictitating membrane, perfused ear artery and strip of pulmonal artery of the rabbit, rat vas deferens), was introduced. In contrast to the nonselective and A-selective MAO inhibitors, as well as to the newly developed selective MAO-B inhibitors (J-508, U-1424), (-)deprenyl was unique in inhibiting tyramine-uptake in all the tests. (-)Deprenyl was found to inhibit the release of acetylcholine in isolated striatal slices of the rat, owing to its blocking effect on the uptake of dopamine. N-methyl-N-propargyl-/2-furyl-1-methyl/-ethylammonium (U-1424), a new selective inhibitor of MAO-B devoid of uptake-inhibitory effect did not significantly influence the ouabain induced striatal acetylcholine release. The release of dopamine from the synaptosomes of the rat striatum was found to be enhanced by clorgyline and tyramine and only slightly influenced by (-)deprenyl. The advantage of the combination of levodopa and (-)deprenyl in the treatment of Parkinson's disease was summarized as follows. Levodopa exerts its therapeutic effect by stimulating the postsynaptic dopaminergic receptors of the caudate interneurons, thereby it suppresses, by also stimulating the presynaptic 'autoreceptors', the activity of nigrostriatal dopaminergic neurons. (-)Deprenyl acts as a activator of the nigrostriatal dopaminergic neurons.  As these neurons contain MAO-B in man, (-)deprenyl increases the dopamine content of the nerve terminals and as a potent inhibitor of the re-uptake of dopamine it intensifies the physiological control on the cholinergic caudate neurons.

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

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