Combined fenobam and amantadine treatment promotes robust antidyskinetic effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate model of Parkinson's disease.
Identifieur interne : 000043 ( France/Analysis ); précédent : 000042; suivant : 000044Combined fenobam and amantadine treatment promotes robust antidyskinetic effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate model of Parkinson's disease.
Auteurs : Wai Kin D. Ko [France] ; Elsa Pioli ; Qin Li ; Steve Mcguire ; Audrey Dufour ; Todd B. Sherer ; Erwan Bezard ; Maurizio F. FacherisSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2014.
English descriptors
- KwdEn :
- Amantadine (therapeutic use), Analysis of Variance, Animals, Antiparkinson Agents (adverse effects), Disease Models, Animal, Dose-Response Relationship, Drug, Drug Therapy, Combination, Dyskinesia, Drug-Induced (drug therapy), Dyskinesia, Drug-Induced (etiology), Excitatory Amino Acid Antagonists (therapeutic use), Female, Imidazoles (therapeutic use), Levodopa (adverse effects), MPTP Poisoning (drug therapy), Macaca fascicularis.
- MESH :
- chemical , adverse effects : Antiparkinson Agents, Levodopa.
- chemical , therapeutic use : Amantadine, Excitatory Amino Acid Antagonists, Imidazoles.
- drug therapy : Dyskinesia, Drug-Induced, MPTP Poisoning.
- etiology : Dyskinesia, Drug-Induced.
- Analysis of Variance, Animals, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Macaca fascicularis.
Abstract
Amantadine, an N-methyl-D-aspartate glutamate receptor antagonist, is currently the only pharmacological treatment for levodopa-induced dyskinesia (LID) in Parkinson's disease (PD), but causes adverse effects on the central nervous system at therapeutic doses. Fenobam, a negative modulator of metabotropic glutamate receptor subtype 5, has recently been reported to attenuate LID in MPTP-treated macaques. The aim of the current study was to investigate the treatment interactions of fenobam and amantadine on LID in the MPTP-treated macaque model of PD. The antidyskinetic and -parkinsonian effects were measured after administration of fenobam (10-30 mg/kg) and amantadine (10-30 mg/kg) alone and in combination. Fenobam (30 mg/kg) and amantadine (30 mg/kg) alone reduced LID, whereas lower doses of either drug did not cause any significant effects. A combined treatment of fenobam and amantadine at subthreshold doses (10 and 20 mg/kg) significantly reduced LID without worsening PD disability. These data suggest that a low-dose combination of fenobam and amantadine can be used for alleviating dyskinesia without causing adverse motor effects. Such combined therapies may offer a new therapeutic strategy for treatment of LID in PD patients.
DOI: 10.1002/mds.25859
PubMed: 24610195
Affiliations:
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pubmed:24610195Le document en format XML
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Ko</name><affiliation wicri:level="4"><nlm:affiliation>Motac Neuroscience Ltd, Manchester, United Kingdom; Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Motac Neuroscience Ltd, Manchester, United Kingdom; Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux</wicri:regionArea><placeName><settlement type="city">Bordeaux</settlement></placeName><orgName type="university">Université de Bordeaux</orgName><placeName><settlement type="city">Bordeaux</settlement><region type="region" nuts="2">Aquitaine</region></placeName></affiliation></author><author><name sortKey="Pioli, Elsa" sort="Pioli, Elsa" uniqKey="Pioli E" first="Elsa" last="Pioli">Elsa Pioli</name></author><author><name sortKey="Li, Qin" sort="Li, Qin" uniqKey="Li Q" first="Qin" last="Li">Qin Li</name></author><author><name sortKey="Mcguire, Steve" sort="Mcguire, Steve" uniqKey="Mcguire S" first="Steve" last="Mcguire">Steve Mcguire</name></author><author><name sortKey="Dufour, Audrey" sort="Dufour, Audrey" uniqKey="Dufour A" first="Audrey" last="Dufour">Audrey Dufour</name></author><author><name sortKey="Sherer, Todd B" sort="Sherer, Todd B" uniqKey="Sherer T" first="Todd B" last="Sherer">Todd B. 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Ko</name><affiliation wicri:level="4"><nlm:affiliation>Motac Neuroscience Ltd, Manchester, United Kingdom; Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Motac Neuroscience Ltd, Manchester, United Kingdom; Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux</wicri:regionArea><placeName><settlement type="city">Bordeaux</settlement></placeName><orgName type="university">Université de Bordeaux</orgName><placeName><settlement type="city">Bordeaux</settlement><region type="region" nuts="2">Aquitaine</region></placeName></affiliation></author><author><name sortKey="Pioli, Elsa" sort="Pioli, Elsa" uniqKey="Pioli E" first="Elsa" last="Pioli">Elsa Pioli</name></author><author><name sortKey="Li, Qin" sort="Li, Qin" uniqKey="Li Q" first="Qin" last="Li">Qin Li</name></author><author><name sortKey="Mcguire, Steve" sort="Mcguire, Steve" uniqKey="Mcguire S" first="Steve" last="Mcguire">Steve Mcguire</name></author><author><name sortKey="Dufour, Audrey" sort="Dufour, Audrey" uniqKey="Dufour A" first="Audrey" last="Dufour">Audrey Dufour</name></author><author><name sortKey="Sherer, Todd B" sort="Sherer, Todd B" uniqKey="Sherer T" first="Todd B" last="Sherer">Todd B. Sherer</name></author><author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name></author><author><name sortKey="Facheris, Maurizio F" sort="Facheris, Maurizio F" uniqKey="Facheris M" first="Maurizio F" last="Facheris">Maurizio F. Facheris</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amantadine (therapeutic use)</term><term>Analysis of Variance</term><term>Animals</term><term>Antiparkinson Agents (adverse effects)</term><term>Disease Models, Animal</term><term>Dose-Response Relationship, Drug</term><term>Drug Therapy, Combination</term><term>Dyskinesia, Drug-Induced (drug therapy)</term><term>Dyskinesia, Drug-Induced (etiology)</term><term>Excitatory Amino Acid Antagonists (therapeutic use)</term><term>Female</term><term>Imidazoles (therapeutic use)</term><term>Levodopa (adverse effects)</term><term>MPTP Poisoning (drug therapy)</term><term>Macaca fascicularis</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Amantadine</term><term>Excitatory Amino Acid Antagonists</term><term>Imidazoles</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Dyskinesia, Drug-Induced</term><term>MPTP Poisoning</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Dyskinesia, Drug-Induced</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Analysis of Variance</term><term>Animals</term><term>Disease Models, Animal</term><term>Dose-Response Relationship, Drug</term><term>Drug Therapy, Combination</term><term>Female</term><term>Macaca fascicularis</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Amantadine, an N-methyl-D-aspartate glutamate receptor antagonist, is currently the only pharmacological treatment for levodopa-induced dyskinesia (LID) in Parkinson's disease (PD), but causes adverse effects on the central nervous system at therapeutic doses. Fenobam, a negative modulator of metabotropic glutamate receptor subtype 5, has recently been reported to attenuate LID in MPTP-treated macaques. The aim of the current study was to investigate the treatment interactions of fenobam and amantadine on LID in the MPTP-treated macaque model of PD. The antidyskinetic and -parkinsonian effects were measured after administration of fenobam (10-30 mg/kg) and amantadine (10-30 mg/kg) alone and in combination. Fenobam (30 mg/kg) and amantadine (30 mg/kg) alone reduced LID, whereas lower doses of either drug did not cause any significant effects. A combined treatment of fenobam and amantadine at subthreshold doses (10 and 20 mg/kg) significantly reduced LID without worsening PD disability. These data suggest that a low-dose combination of fenobam and amantadine can be used for alleviating dyskinesia without causing adverse motor effects. Such combined therapies may offer a new therapeutic strategy for treatment of LID in PD patients.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Aquitaine</li></region><settlement><li>Bordeaux</li></settlement><orgName><li>Université de Bordeaux</li></orgName></list><tree><noCountry><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name><name sortKey="Dufour, Audrey" sort="Dufour, Audrey" uniqKey="Dufour A" first="Audrey" last="Dufour">Audrey Dufour</name><name sortKey="Facheris, Maurizio F" sort="Facheris, Maurizio F" uniqKey="Facheris M" first="Maurizio F" last="Facheris">Maurizio F. Facheris</name><name sortKey="Li, Qin" sort="Li, Qin" uniqKey="Li Q" first="Qin" last="Li">Qin Li</name><name sortKey="Mcguire, Steve" sort="Mcguire, Steve" uniqKey="Mcguire S" first="Steve" last="Mcguire">Steve Mcguire</name><name sortKey="Pioli, Elsa" sort="Pioli, Elsa" uniqKey="Pioli E" first="Elsa" last="Pioli">Elsa Pioli</name><name sortKey="Sherer, Todd B" sort="Sherer, Todd B" uniqKey="Sherer T" first="Todd B" last="Sherer">Todd B. Sherer</name></noCountry><country name="France"><noRegion><name sortKey="Ko, Wai Kin D" sort="Ko, Wai Kin D" uniqKey="Ko W" first="Wai Kin D" last="Ko">Wai Kin D. Ko</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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