The mGluR5 negative allosteric modulator dipraglurant reduces dyskinesia in the MPTP macaque model.
Mov Disord.. 2014-05-27; 29(8): 1074-1079
DOI: 10.1002/mds.25920
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1. Mov Disord. 2014 Jul;29(8):1074-9. doi: 10.1002/mds.25920. Epub 2014 May 27.
The mGluR5 negative allosteric modulator dipraglurant reduces dyskinesia in the
MPTP macaque model.
Bezard E(1), Pioli EY, Li Q, Girard F, Mutel V, Keywood C, Tison F, Rascol O,
Poli SM.
Author information:
(1)Motac neuroscience, Manchester, UK; Université de Bordeaux, Institut des
Maladies Neurodégénératives, UMR 5293, Bordeaux, France; CNRS, Institut des
Maladies Neurodégénératives, UMR 5293, Bordeaux, France; Service de Neurologie,
CHU de Bordeaux, Pessac, France; Institute of Laboratory Animal Sciences, China
Academy of Medical Sciences, Beijing, China.
BACKGROUND: Blocking metabotropic glutamate receptor type 5 (mGluR5) has been
proposed as a target for levodopa-induced dyskinesias (LID) in Parkinson’s
disease (PD). We assessed the effect on LID of dipraglurant, a potent selective
mGluR5 receptor negative allosteric modulator in the gold-standard LID macaque
model.
METHODS: Dipraglurant (3, 10, and 30 mg/kg, by mouth) was tested in the
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) macaque model of LID in a
four-way crossover, single-dose, controlled study (n = 8).
RESULTS: Dipraglurant inhibited dyskinesias in the LID macaque model, with best
effect reached at 30 mg/kg dose with no alteration of levodopa efficacy.
CONCLUSION: Acute challenges of dipraglurant were efficacious on choreic and
dystonic LID in the MPTP-macaque model. Dipraglurant pharmacokinetic variables
were similar to those of levodopa, suggesting that both drugs can be
co-administered simultaneously in further studies.
© 2014 International Parkinson and Movement Disorder Society.
DOI: 10.1002/mds.25920
PMID: 24865335 [Indexed for MEDLINE]