A mGluR5 antagonist under clinical development improves L-DOPA-induced dyskinesia in parkinsonian rats and monkeys.
Neurobiology of Disease. 2010-09-01; 39(3): 352-361
DOI: 10.1016/j.nbd.2010.05.001
Read on PubMed
1. Neurobiol Dis. 2010 Sep;39(3):352-61. doi: 10.1016/j.nbd.2010.05.001. Epub 2010
May 7.
A mGluR5 antagonist under clinical development improves L-DOPA-induced dyskinesia
in parkinsonian rats and monkeys.
Rylander D(1), Iderberg H, Li Q, Dekundy A, Zhang J, Li H, Baishen R, Danysz W,
Bezard E, Cenci MA.
Author information:
(1)Basal Ganglia Pathophysiology Unit, Department of Experimental Medical
Science, Lund University, BMC F11, Lund, Sweden.
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 Parkinson’s
disease. 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 represents a good candidate for
antidyskinetic treatment in Parkinson’s disease.
DOI: 10.1016/j.nbd.2010.05.001
PMID: 20452425 [Indexed for MEDLINE]