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.

Wai Kin D. Ko, Elsa Pioli, Qin Li, Steve McGuire, Audrey Dufour, Todd B. Sherer, Erwan Bezard, Maurizio F. Facheris
Mov Disord.. 2014-03-07; 29(6): 772-779
DOI: 10.1002/mds.25859

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1. Mov Disord. 2014 May;29(6):772-9. doi: 10.1002/mds.25859. Epub 2014 Mar 7.

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.

Ko WK(1), Pioli E, Li Q, McGuire S, Dufour A, Sherer TB, Bezard E, Facheris MF.

Author information:
(1)Motac Neuroscience Ltd, Manchester, United Kingdom; Université de Bordeaux,
Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France; CNRS,
Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.

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.

DOI: 10.1002/mds.25859
PMID: 24610195 [Indexed for MEDLINE]

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