Effect of a selective glutamate antagonist on L-dopa-induced dyskinesias in drug-naive parkinsonian monkeys.

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.

• 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)

Chemical References

• Benzoxazoles
• Excitatory Amino Acid Antagonists
• NR1A NMDA receptor, rat
• NR2B NMDA receptor
• Piperidines
• Receptors, N-Methyl-D-Aspartate
• Glutamic Acid
• Levodopa
• besonprodil

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