A mGluR5 antagonist under clinical development improves L-DOPA-induced dyskinesia in parkinsonian rats and monkeys.
Författare
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.
Avdelning/ar
Publiceringsår
2010
Språk
Engelska
Sidor
352-361
Publikation/Tidskrift/Serie
Neurobiology of Disease
Volym
39
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Elsevier
Ämne
- Neurosciences
Status
Published
Forskningsgrupp
- Basal Ganglia Pathophysiology
ISBN/ISSN/Övrigt
- ISSN: 0969-9961