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.

Keywords

• Parkinson's disease
• Prevention
• l-dopa-induced dyskinesias
• CI-1041
• NMDA receptor
• MPTP monkeys