Funding agencies: This research was supported by the Edmonds Bequest for Parkinson's Disease Research.
Article first published online: 23 SEP 2011
Copyright © 2011 Movement Disorder Society
Volume 26, Issue 13, pages 2354–2363, November 2011
How to Cite
Kobylecki, C., Hill, M. P., Crossman, A. R. and Ravenscroft, P. (2011), Synergistic antidyskinetic effects of topiramate and amantadine in animal models of Parkinson's disease. Mov. Disord., 26: 2354–2363. doi: 10.1002/mds.23867
Relevant conflicts of interest/financial disclosures: Alan R. Crossman holds equity in a company holding a use patent for topiramate in L-dopa-induced dyskinesia.
Full financial disclosures and author roles may be found in the online version of this article.
- Issue published online: 22 NOV 2011
- Article first published online: 23 SEP 2011
- Manuscript Accepted: 15 JUN 2011
- Manuscript Revised: 8 JUN 2011
- Manuscript Received: 29 MAR 2011
- 6-OHDA-lesioned rat;
- MPTP-lesioned primate
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. © 2011 Movement Disorder Society