Combined Fenobam and Amantadine Treatment Promotes Robust Antidyskinetic Effects in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP)-Lesioned Primate Model of Parkinson's Disease
Amantadine is currently the only drug prescribed to PD patients for counteracting levodopa-induced dyskinesia (LID) but therapeutic doses are not always efficacious and might lead to side effects. Research has validated that inhibition of the receptor mGluR5 can improve LID. In this study, (i) amantadine and (ii) fenobam, a negative modulator of this mGluR5 receptor reduce LID in a pre-clinical model of PD when given alone. When combining lower doses of the two drugs, the additive effect was clinically significant, drastically reducing LID. These data suggest that a combination of mGluR5 inhibitors and amantadine in lower doses than what currently used might reduce levodopa-induced dyskinesia without diminishing the antiparkinsonian effect of levodopa.
Authors: Wai Kin D. Ko, Elsa Pioli, Qin Li, Steve McGuire, Audrey Dufour, Todd B. Sherer, Erwan Bezard, Maurizio F. Facheris