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

Research output: Contribution to journalArticle

174 Citations (Scopus)

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. By the aid of N-methyl-N-propargyl-/l-indenyl/-ammonium. HCl (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 stimulating also the presynaptic "autoreceptors", the activity of nigrostriatal dopaminergic neurons. (-)Deprenyl acts as an 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.

Original languageEnglish
Pages (from-to)177-198
Number of pages22
JournalJournal of Neural Transmission
Volume43
Issue number3-4
DOIs
Publication statusPublished - Sep 1978

Fingerprint

Selegiline
Parkinson Disease
Monoamine Oxidase
Monoamine Oxidase Inhibitors
Tyramine
Clorgyline
Corpus Striatum
Dopamine
Dopaminergic Neurons
Levodopa
Acetylcholine
Arteries
Dopamine Uptake Inhibitors
Nictitating Membrane
Neurons
Autoreceptors
Cholinergic Neurons
Vas Deferens
Nerve Endings
Synaptosomes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

The possible mechanisms of action of (-)deprenyl in Parkinson's disease. / Knoll, J.

In: Journal of Neural Transmission, Vol. 43, No. 3-4, 09.1978, p. 177-198.

Research output: Contribution to journalArticle

@article{ca99f0001f9d462fb744989812d2103d,
title = "The possible mechanisms of action of (-)deprenyl in Parkinson's disease",
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. By the aid of N-methyl-N-propargyl-/l-indenyl/-ammonium. HCl (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 stimulating also the presynaptic {"}autoreceptors{"}, the activity of nigrostriatal dopaminergic neurons. (-)Deprenyl acts as an 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.",
author = "J. Knoll",
year = "1978",
month = "9",
doi = "10.1007/BF01246955",
language = "English",
volume = "43",
pages = "177--198",
journal = "Journal of Neural Transmission",
issn = "0300-9564",
publisher = "Springer Verlag",
number = "3-4",

}

TY - JOUR

T1 - The possible mechanisms of action of (-)deprenyl in Parkinson's disease

AU - Knoll, J.

PY - 1978/9

Y1 - 1978/9

N2 - (-)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. By the aid of N-methyl-N-propargyl-/l-indenyl/-ammonium. HCl (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 stimulating also the presynaptic "autoreceptors", the activity of nigrostriatal dopaminergic neurons. (-)Deprenyl acts as an 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.

AB - (-)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. By the aid of N-methyl-N-propargyl-/l-indenyl/-ammonium. HCl (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 stimulating also the presynaptic "autoreceptors", the activity of nigrostriatal dopaminergic neurons. (-)Deprenyl acts as an 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.

UR - http://www.scopus.com/inward/record.url?scp=0018128143&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018128143&partnerID=8YFLogxK

U2 - 10.1007/BF01246955

DO - 10.1007/BF01246955

M3 - Article

C2 - 745011

AN - SCOPUS:0018128143

VL - 43

SP - 177

EP - 198

JO - Journal of Neural Transmission

JF - Journal of Neural Transmission

SN - 0300-9564

IS - 3-4

ER -