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.