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 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.
Hadj Tahar
Abdallah
A
Neuroscience Research Unit (RC 9800), CHUL, Laval University Research Center, Ste-Foy, Québec, Canada G1V 4G2.
Grégoire
Laurent
L
Darré
Aurélie
A
Bélanger
Nancy
N
Meltzer
Leonard
L
Bédard
Paul J
PJ
D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004347:Drug Interactions; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D007980:Levodopa / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D008252:Macaca fascicularis; D010300:Parkinson Disease / Q000188:drug therapy; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016896:Treatment Outcome
D001583:Benzoxazoles; D018691:Excitatory Amino Acid Antagonists; C473649:NR1A NMDA receptor, rat; C121001:NR2B NMDA receptor; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D007980:Levodopa; C481484:besonprodil