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The antiepileptic drug topiramate, which blocks \u03b1\u2010amino\u20103\u2010hydroxy\u20105\u2010methyl\u20104\u2010isoxazolepropionic 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 <jats:sc>L<\/jats:sc>\u2010dopa\u2010induced dyskinesia. The effects of topiramate (5\u201320 mg\/kg) and amantadine (5\u201320 mg\/kg) on abnormal involuntary movements (the rat homologue of dyskinesia) and Rotarod performance were assessed alone and in combination in the 6\u2010hydroxydopamine\u2010lesioned rat following chronic <jats:sc>L<\/jats:sc>\u2010dopa treatment. Dyskinesia, parkinsonian disability, and \u201con\u2010time\u201d were assessed in the MPTP\u2010lesioned nonhuman primate following administration of topiramate (5\u201320 mg\/kg) and amantadine (0.1\u20131.0 mg\/kg) alone and in combination. Topiramate and amantadine dose\u2010dependently reduced dyskinesia in the 6\u2010hydroxydopamine\u2010lesioned rat, whereas topiramate reduced Rotarod performance; there was no effect on parkinsonian disability in the MPTP\u2010lesioned 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\u2010hydroxydopamine\u2010lesioned rat, with no worsening of motor performance; this effect was confirmed in the MPTP\u2010lesioned nonhuman primate, with a selective reduction in \u201cbad on\u2010time.\u201d These data confirm the antidyskinetic potential of topiramate and suggest that combination with low\u2010dose amantadine may allow better reduction of dyskinesia with no adverse motor effects. \u00a9 2011 Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.23867","type":"journal-article","created":{"date-parts":[[2011,9,27]],"date-time":"2011-09-27T19:05:36Z","timestamp":1317150336000},"page":"2354-2363","source":"Crossref","is-referenced-by-count":45,"title":["Synergistic antidyskinetic effects of topiramate and amantadine in animal models of Parkinson's 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