Effect of a selective glutamate antagonist on L-dopa-induced dyskinesias in drug-naive parkinsonian monkeys.
Identifieur interne : 002B88 ( Main/Exploration ); précédent : 002B87; suivant : 002B89Effect of a selective glutamate antagonist on L-dopa-induced dyskinesias in drug-naive parkinsonian monkeys.
Auteurs : Abdallah Hadj Tahar [Canada] ; Laurent Grégoire ; Aurélie Darré ; Nancy Bélanger ; Leonard Meltzer ; Paul J. BédardSource :
- Neurobiology of disease [ 0969-9961 ] ; 2004.
English descriptors
- KwdEn :
- Animals, Benzoxazoles (pharmacology), Benzoxazoles (therapeutic use), Corpus Striatum (drug effects), Corpus Striatum (metabolism), Corpus Striatum (physiopathology), Disease Models, Animal, Drug Interactions, Dyskinesia, Drug-Induced (drug therapy), Dyskinesia, Drug-Induced (metabolism), Dyskinesia, Drug-Induced (physiopathology), Excitatory Amino Acid Antagonists (pharmacology), Excitatory Amino Acid Antagonists (therapeutic use), Female, Glutamic Acid (metabolism), Levodopa (adverse effects), Levodopa (antagonists & inhibitors), Macaca fascicularis, Parkinson Disease (drug therapy), Piperidines (pharmacology), Piperidines (therapeutic use), Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors), Receptors, N-Methyl-D-Aspartate (metabolism), Treatment Outcome.
- MESH :
- chemical , adverse effects : Levodopa.
- chemical , antagonists & inhibitors : Levodopa, Receptors, N-Methyl-D-Aspartate.
- chemical , metabolism : Glutamic Acid, Receptors, N-Methyl-D-Aspartate.
- chemical , pharmacology : Benzoxazoles, Excitatory Amino Acid Antagonists, Piperidines.
- chemical , therapeutic use : Benzoxazoles, Excitatory Amino Acid Antagonists, Piperidines.
- drug effects : Corpus Striatum.
- drug therapy : Dyskinesia, Drug-Induced, Parkinson Disease.
- metabolism : Corpus Striatum, Dyskinesia, Drug-Induced.
- physiopathology : Corpus Striatum, Dyskinesia, Drug-Induced.
- Animals, Disease Models, Animal, Drug Interactions, Female, Macaca fascicularis, Treatment Outcome.
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.
DOI: 10.1016/j.nbd.2003.10.007
PubMed: 15006686
Affiliations:
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Bédard</name></author></analytic><series><title level="j">Neurobiology of disease</title><idno type="ISSN">0969-9961</idno><imprint><date when="2004" type="published">2004</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Benzoxazoles (pharmacology)</term><term>Benzoxazoles (therapeutic use)</term><term>Corpus Striatum (drug effects)</term><term>Corpus Striatum (metabolism)</term><term>Corpus Striatum (physiopathology)</term><term>Disease Models, Animal</term><term>Drug Interactions</term><term>Dyskinesia, Drug-Induced (drug therapy)</term><term>Dyskinesia, Drug-Induced (metabolism)</term><term>Dyskinesia, Drug-Induced (physiopathology)</term><term>Excitatory Amino Acid Antagonists (pharmacology)</term><term>Excitatory Amino Acid Antagonists (therapeutic use)</term><term>Female</term><term>Glutamic Acid (metabolism)</term><term>Levodopa (adverse effects)</term><term>Levodopa (antagonists & inhibitors)</term><term>Macaca fascicularis</term><term>Parkinson Disease (drug therapy)</term><term>Piperidines (pharmacology)</term><term>Piperidines (therapeutic use)</term><term>Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)</term><term>Receptors, N-Methyl-D-Aspartate (metabolism)</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Levodopa</term><term>Receptors, N-Methyl-D-Aspartate</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Glutamic Acid</term><term>Receptors, N-Methyl-D-Aspartate</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Benzoxazoles</term><term>Excitatory Amino Acid Antagonists</term><term>Piperidines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Benzoxazoles</term><term>Excitatory Amino Acid Antagonists</term><term>Piperidines</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Corpus Striatum</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Dyskinesia, Drug-Induced</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Corpus Striatum</term><term>Dyskinesia, Drug-Induced</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Corpus Striatum</term><term>Dyskinesia, Drug-Induced</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Drug Interactions</term><term>Female</term><term>Macaca fascicularis</term><term>Treatment Outcome</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J" last="Bédard">Paul J. Bédard</name><name sortKey="Belanger, Nancy" sort="Belanger, Nancy" uniqKey="Belanger N" first="Nancy" last="Bélanger">Nancy Bélanger</name><name sortKey="Darre, Aurelie" sort="Darre, Aurelie" uniqKey="Darre A" first="Aurélie" last="Darré">Aurélie Darré</name><name sortKey="Gregoire, Laurent" sort="Gregoire, Laurent" uniqKey="Gregoire L" first="Laurent" last="Grégoire">Laurent Grégoire</name><name sortKey="Meltzer, Leonard" sort="Meltzer, Leonard" uniqKey="Meltzer L" first="Leonard" last="Meltzer">Leonard Meltzer</name></noCountry><country name="Canada"><noRegion><name sortKey="Hadj Tahar, Abdallah" sort="Hadj Tahar, Abdallah" uniqKey="Hadj Tahar A" first="Abdallah" last="Hadj Tahar">Abdallah Hadj Tahar</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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