Journal
NEUROBIOLOGY OF DISEASE
Volume 39, Issue 3, Pages 352-361Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2010.05.001
Keywords
Dopamine replacement; Motor complication; Rotarod; Rotation; AIMs; Involuntary movements; Dopamine denervation; mGluR; Glutamate receptor; Neurotransmitter; Striatum; LID
Categories
Funding
- Michael J. Fox Foundation for Parkinson's Research
- Swedish National Research Council
- European Community [2229181]
Ask authors/readers for more resources
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 30 mg/kg in rats and 10 mg/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-naive 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. (C) 2010 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available