Synergistic Antidyskinetic Effects of Topiramate and Amantadine in Animal Models of Parkinson's Disease
Identifieur interne : 001915 ( Main/Exploration ); précédent : 001914; suivant : 001916Synergistic Antidyskinetic Effects of Topiramate and Amantadine in Animal Models of Parkinson's Disease
Auteurs : Christopher Kobylecki [Royaume-Uni] ; Michael P. Hill [Canada] ; Alan R. Crossman [Royaume-Uni] ; Paula Ravenscroft [Royaume-Uni, Canada]Source :
- Movement disorders [ 0885-3185 ] ; 2011.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
L-Dopa-induced dyskinesia in patients with Parkinson's disease can be alleviated by amantadine, an antagonist at N-methyl-D-aspartate glutamate receptors. The antiepileptic drug topiramate, which blocks α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, has also been shown to reduce dyskinesia. The purpose of this study was to examine the behavioral pharmacology of topiramate alone and in combination with amantadine in animal models of PD and L-dopa-induced dyskinesia. The effects of topiramate (5-20 mg/kg) and amantadine (5-20 mg/kg) on abnormal involuntary movements (the rat homologue of dyskinesia) and Rotarod performance were assessed alone and in combination in the 6-hydroxydopamine-lesioned rat following chronic L-dopa treatment. Dyskinesia, parkinsonian disability, and "on-time" were assessed in the MPTP-lesioned nonhuman primate following administration of topiramate (5-20 mg/kg) and amantadine (0.1-1.0 mg/kg) alone and in combination. Topiramate and amantadine dose-dependently reduced dyskinesia in the 6-hydroxydopamine-lesioned rat, whereas topiramate reduced Rotarod performance; there was no effect on parkinsonian disability in the MPTP-lesioned nonhuman primate, in which both drugs reduced dyskinesia. Topiramate and amantadine exhibited differential antidyskinetic effects on dyskinesia elicited by the dopamine D1 receptor agonist SKF 38393 (2 mg/kg). Subthreshold doses of both drugs in combination had a synergistic effect on dyskinesia in the 6-hydroxydopamine-lesioned rat, with no worsening of motor performance; this effect was confirmed in the MPTP-lesioned nonhuman primate, with a selective reduction in "bad on-time." These data confirm the antidyskinetic potential of topiramate and suggest that combination with low-dose amantadine may allow better reduction of dyskinesia with no adverse motor effects.
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Hill</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Toronto Western Research Institute, Toronto Western Hospital, University Health Network</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto, Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Crossman, Alan R" sort="Crossman, Alan R" uniqKey="Crossman A" first="Alan R." last="Crossman">Alan R. Crossman</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Faculty of Life Sciences, University of Manchester</s1><s2>Manchester</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Manchester</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Manchester</region><settlement type="city">Manchester</settlement></placeName><orgName type="university">Université de Manchester</orgName></affiliation></author><author><name sortKey="Ravenscroft, Paula" sort="Ravenscroft, Paula" uniqKey="Ravenscroft P" first="Paula" last="Ravenscroft">Paula Ravenscroft</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Faculty of Life Sciences, University of Manchester</s1><s2>Manchester</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Manchester</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Manchester</region><settlement type="city">Manchester</settlement></placeName><orgName type="university">Université de Manchester</orgName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Toronto Western Research Institute, Toronto Western Hospital, University Health Network</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto, Ontario</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amantadine</term><term>Animal</term><term>Animal model</term><term>Dyskinesia</term><term>Nervous system diseases</term><term>Parkinson disease</term><term>Primates</term><term>Rat</term><term>Topiramate</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term><term>Dyskinésie</term><term>Pathologie du système nerveux</term><term>Topiramate</term><term>Amantadine</term><term>Modèle animal</term><term>Animal</term><term>Rat</term><term>Primates</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">L-Dopa-induced dyskinesia in patients with Parkinson's disease can be alleviated by amantadine, an antagonist at N-methyl-D-aspartate glutamate receptors. The antiepileptic drug topiramate, which blocks α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, has also been shown to reduce dyskinesia. The purpose of this study was to examine the behavioral pharmacology of topiramate alone and in combination with amantadine in animal models of PD and L-dopa-induced dyskinesia. The effects of topiramate (5-20 mg/kg) and amantadine (5-20 mg/kg) on abnormal involuntary movements (the rat homologue of dyskinesia) and Rotarod performance were assessed alone and in combination in the 6-hydroxydopamine-lesioned rat following chronic L-dopa treatment. Dyskinesia, parkinsonian disability, and "on-time" were assessed in the MPTP-lesioned nonhuman primate following administration of topiramate (5-20 mg/kg) and amantadine (0.1-1.0 mg/kg) alone and in combination. Topiramate and amantadine dose-dependently reduced dyskinesia in the 6-hydroxydopamine-lesioned rat, whereas topiramate reduced Rotarod performance; there was no effect on parkinsonian disability in the MPTP-lesioned nonhuman primate, in which both drugs reduced dyskinesia. Topiramate and amantadine exhibited differential antidyskinetic effects on dyskinesia elicited by the dopamine D1 receptor agonist SKF 38393 (2 mg/kg). Subthreshold doses of both drugs in combination had a synergistic effect on dyskinesia in the 6-hydroxydopamine-lesioned rat, with no worsening of motor performance; this effect was confirmed in the MPTP-lesioned nonhuman primate, with a selective reduction in "bad on-time." These data confirm the antidyskinetic potential of topiramate and suggest that combination with low-dose amantadine may allow better reduction of dyskinesia with no adverse motor effects.</div></front></TEI><affiliations><list><country><li>Canada</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Grand Manchester</li></region><settlement><li>Manchester</li></settlement><orgName><li>Université de Manchester</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Kobylecki, Christopher" sort="Kobylecki, Christopher" uniqKey="Kobylecki C" first="Christopher" last="Kobylecki">Christopher Kobylecki</name></region><name sortKey="Crossman, Alan R" sort="Crossman, Alan R" uniqKey="Crossman A" first="Alan R." last="Crossman">Alan R. Crossman</name><name sortKey="Kobylecki, Christopher" sort="Kobylecki, Christopher" uniqKey="Kobylecki C" first="Christopher" last="Kobylecki">Christopher Kobylecki</name><name sortKey="Kobylecki, Christopher" sort="Kobylecki, Christopher" uniqKey="Kobylecki C" first="Christopher" last="Kobylecki">Christopher Kobylecki</name><name sortKey="Ravenscroft, Paula" sort="Ravenscroft, Paula" uniqKey="Ravenscroft P" first="Paula" last="Ravenscroft">Paula Ravenscroft</name></country><country name="Canada"><noRegion><name sortKey="Hill, Michael P" sort="Hill, Michael P" uniqKey="Hill M" first="Michael P." last="Hill">Michael P. Hill</name></noRegion><name sortKey="Ravenscroft, Paula" sort="Ravenscroft, Paula" uniqKey="Ravenscroft P" first="Paula" last="Ravenscroft">Paula Ravenscroft</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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