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A mGluR5 antagonist under clinical development improves L-DOPA-induced dyskinesia in parkinsonian rats and monkeys.

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Author

Summary, in English

L-DOPA remains the gold-standard treatment for Parkinson's disease but causes motor fluctuations and dyskinesia. Metabotropic glutamate receptor type 5 (mGluR5) has been proposed as a target for antidyskinetic therapies. Here, we evaluate the effects of fenobam, a noncompetitive mGluR5 antagonist already tested in humans, using rodent and nonhuman primate models of L-DOPA-induced dyskinesia. In both animal models, acute administration of fenobam attenuated the L-DOPA-induced abnormal involuntary movements (50-70% reduction at the doses of 30mg/kg in rats and 10mg/kg in monkeys). The effect consisted in a reduction of peak-dose dyskinesia, whereas the end-dose phase was not affected. Chronic administration of fenobam to previously drug-naïve animals (de novo treatment) attenuated the development of peak-dose dyskinesia without compromising the anti-parkinsonian effect of L-DOPA. In addition, fenobam prolonged the motor stimulant effect of L-DOPA. We conclude that fenobam acts similarly in rat and primate models of L-DOPA-induced dyskinesia and that it represents a good candidate for antidyskinetic treatment in Parkinson's disease.

Publishing year

2010

Language

English

Pages

352-361

Publication/Series

Neurobiology of Disease

Volume

39

Document type

Journal article

Publisher

Elsevier

Topic

  • Neurosciences

Status

Published

Research group

  • Basal Ganglia Pathophysiology

ISBN/ISSN/Other

  • ISSN: 0969-9961