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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

Authors


  • Funding agencies: This study was supported by the Michael J. Fox Foundation.

  • Relevant conflicts of interest/financial disclosures: E.B. has an equity stake in Motac Holding Ltd and receives consultancy payments from Motac Neuroscience Ltd. and has current grant support from Agence Nationale de la Recherche, China Science Fund, the Michael J. Fox Foundation (MJFF), FP7 from EU, France Parkinson, Fondation de France, and Cariplo Foundation. M.F.F., A.D., and T.S. are employees of the MJFF, a nonprofit organization. W.K.K., E.P., Q.L., and S.M. are employees of Motac Neuroscience Ltd.

  • Full financial disclosures and author roles may be found in the online version of this article.

ABSTRACT

Amantadine, an N-methyl-D-aspartate glutamate receptor antagonist, is currently the only pharmacological treatment for levodopa-induced dyskinesia (LID) in Parkinson's disease (PD), but causes adverse effects on the central nervous system at therapeutic doses. Fenobam, a negative modulator of metabotropic glutamate receptor subtype 5, has recently been reported to attenuate LID in MPTP-treated macaques. The aim of the current study was to investigate the treatment interactions of fenobam and amantadine on LID in the MPTP-treated macaque model of PD. The antidyskinetic and -parkinsonian effects were measured after administration of fenobam (10-30 mg/kg) and amantadine (10-30 mg/kg) alone and in combination. Fenobam (30 mg/kg) and amantadine (30 mg/kg) alone reduced LID, whereas lower doses of either drug did not cause any significant effects. A combined treatment of fenobam and amantadine at subthreshold doses (10 and 20 mg/kg) significantly reduced LID without worsening PD disability. These data suggest that a low-dose combination of fenobam and amantadine can be used for alleviating dyskinesia without causing adverse motor effects. Such combined therapies may offer a new therapeutic strategy for treatment of LID in PD patients. © 2014 International Parkinson and Movement Disorder Society

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