Effect of a selective glutamate antagonist on l-dopa-induced dyskinesias in drug-naive parkinsonian monkeys
Alterations of striatal glutamate receptors are believed to be responsible, at least in part, for the pathogenesis of l-dopa-induced dyskinesias (LID). To evaluate whether co-administration of CI-1041, a novel NMDA receptor antagonist selective for the NR1A/NR2B subtype, with l-dopa might prevent th...
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doaj-174938850bc84fccb7c87fec083593f22021-03-20T04:49:01ZengElsevierNeurobiology of Disease1095-953X2004-03-01152171176Effect of a selective glutamate antagonist on l-dopa-induced dyskinesias in drug-naive parkinsonian monkeysAbdallah Hadj Tahar0Laurent Grégoire1Aurélie Darré2Nancy Bélanger3Leonard Meltzer4Paul J Bédard5Neuroscience Research Unit (RC 9800), CHUL, Laval University Research Center, Ste-Foy, Québec, Canada G1V 4G2; Pfizer Global Research and Development, Parke-Davis, Warner-Lambert Co., Ann Arbor, MI, 48104, USANeuroscience Research Unit (RC 9800), CHUL, Laval University Research Center, Ste-Foy, Québec, Canada G1V 4G2; Pfizer Global Research and Development, Parke-Davis, Warner-Lambert Co., Ann Arbor, MI, 48104, USANeuroscience Research Unit (RC 9800), CHUL, Laval University Research Center, Ste-Foy, Québec, Canada G1V 4G2; Pfizer Global Research and Development, Parke-Davis, Warner-Lambert Co., Ann Arbor, MI, 48104, USANeuroscience Research Unit (RC 9800), CHUL, Laval University Research Center, Ste-Foy, Québec, Canada G1V 4G2; Pfizer Global Research and Development, Parke-Davis, Warner-Lambert Co., Ann Arbor, MI, 48104, USANeuroscience Research Unit (RC 9800), CHUL, Laval University Research Center, Ste-Foy, Québec, Canada G1V 4G2; Pfizer Global Research and Development, Parke-Davis, Warner-Lambert Co., Ann Arbor, MI, 48104, USANeuroscience Research Unit (RC 9800), CHUL, Laval University Research Center, Ste-Foy, Québec, Canada G1V 4G2; Pfizer Global Research and Development, Parke-Davis, Warner-Lambert Co., Ann Arbor, MI, 48104, USAAlterations of striatal glutamate receptors are believed to be responsible, at least in part, for the pathogenesis of l-dopa-induced dyskinesias (LID). To evaluate whether co-administration of CI-1041, a novel NMDA receptor antagonist selective for the NR1A/NR2B subtype, with l-dopa might prevent the appearance of this side effect, eight de novo parkinsonian monkeys were treated chronically orally with either l-dopa alone or l-dopa plus CI-1041 (n= 4 for each group). After 4 weeks of treatment with l-dopa alone, all four animals developed moderate dyskinesias either choreic or dystonic in nature. CI-1041 co-treatment completely prevented the induction of dyskinesias in three animals and only one monkey developed mild dyskinesias at the end of the fourth week of treatment in the l-dopa + CI-1041 group. The magnitude and duration of the antiparkinsonian action of l-dopa was similar in both groups. These results suggest that selective NMDA receptor antagonism may be interesting for managing LID in Parkinson's disease patients.http://www.sciencedirect.com/science/article/pii/S0969996103002122Parkinson's diseasePreventionl-dopa-induced dyskinesiasCI-1041NMDA receptorMPTP monkeys |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Abdallah Hadj Tahar Laurent Grégoire Aurélie Darré Nancy Bélanger Leonard Meltzer Paul J Bédard |
spellingShingle |
Abdallah Hadj Tahar Laurent Grégoire Aurélie Darré Nancy Bélanger Leonard Meltzer Paul J Bédard Effect of a selective glutamate antagonist on l-dopa-induced dyskinesias in drug-naive parkinsonian monkeys Neurobiology of Disease Parkinson's disease Prevention l-dopa-induced dyskinesias CI-1041 NMDA receptor MPTP monkeys |
author_facet |
Abdallah Hadj Tahar Laurent Grégoire Aurélie Darré Nancy Bélanger Leonard Meltzer Paul J Bédard |
author_sort |
Abdallah Hadj Tahar |
title |
Effect of a selective glutamate antagonist on l-dopa-induced dyskinesias in drug-naive parkinsonian monkeys |
title_short |
Effect of a selective glutamate antagonist on l-dopa-induced dyskinesias in drug-naive parkinsonian monkeys |
title_full |
Effect of a selective glutamate antagonist on l-dopa-induced dyskinesias in drug-naive parkinsonian monkeys |
title_fullStr |
Effect of a selective glutamate antagonist on l-dopa-induced dyskinesias in drug-naive parkinsonian monkeys |
title_full_unstemmed |
Effect of a selective glutamate antagonist on l-dopa-induced dyskinesias in drug-naive parkinsonian monkeys |
title_sort |
effect of a selective glutamate antagonist on l-dopa-induced dyskinesias in drug-naive parkinsonian monkeys |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2004-03-01 |
description |
Alterations of striatal glutamate receptors are believed to be responsible, at least in part, for the pathogenesis of l-dopa-induced dyskinesias (LID). To evaluate whether co-administration of CI-1041, a novel NMDA receptor antagonist selective for the NR1A/NR2B subtype, with l-dopa might prevent the appearance of this side effect, eight de novo parkinsonian monkeys were treated chronically orally with either l-dopa alone or l-dopa plus CI-1041 (n= 4 for each group). After 4 weeks of treatment with l-dopa alone, all four animals developed moderate dyskinesias either choreic or dystonic in nature. CI-1041 co-treatment completely prevented the induction of dyskinesias in three animals and only one monkey developed mild dyskinesias at the end of the fourth week of treatment in the l-dopa + CI-1041 group. The magnitude and duration of the antiparkinsonian action of l-dopa was similar in both groups. These results suggest that selective NMDA receptor antagonism may be interesting for managing LID in Parkinson's disease patients. |
topic |
Parkinson's disease Prevention l-dopa-induced dyskinesias CI-1041 NMDA receptor MPTP monkeys |
url |
http://www.sciencedirect.com/science/article/pii/S0969996103002122 |
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