Abstract |
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.
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Authors | Abdallah Hadj Tahar, Laurent Grégoire, Aurélie Darré, Nancy Bélanger, Leonard Meltzer, Paul J Bédard |
Journal | Neurobiology of disease
(Neurobiol Dis)
Vol. 15
Issue 2
Pg. 171-6
(Mar 2004)
ISSN: 0969-9961 [Print] United States |
PMID | 15006686
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Benzoxazoles
- Excitatory Amino Acid Antagonists
- NR1A NMDA receptor, rat
- NR2B NMDA receptor
- Piperidines
- Receptors, N-Methyl-D-Aspartate
- Glutamic Acid
- Levodopa
- besonprodil
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Topics |
- Animals
- Benzoxazoles
(pharmacology, therapeutic use)
- Corpus Striatum
(drug effects, metabolism, physiopathology)
- Disease Models, Animal
- Drug Interactions
- Dyskinesia, Drug-Induced
(drug therapy, metabolism, physiopathology)
- Excitatory Amino Acid Antagonists
(pharmacology, therapeutic use)
- Female
- Glutamic Acid
(metabolism)
- Levodopa
(adverse effects, antagonists & inhibitors)
- Macaca fascicularis
- Parkinson Disease
(drug therapy)
- Piperidines
(pharmacology, therapeutic use)
- Receptors, N-Methyl-D-Aspartate
(antagonists & inhibitors, metabolism)
- Treatment Outcome
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