Premium
The mGluR5 negative allosteric modulator dipraglurant reduces dyskinesia in the MPTP macaque model
Author(s) -
Bezard Erwan,
Pioli Elsa Y.,
Li Qin,
Girard Françoise,
Mutel Vincent,
Keywood Charlotte,
Tison Francois,
Rascol Olivier,
Poli Sonia M.
Publication year - 2014
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.25920
Subject(s) - macaque , mptp , metabotropic glutamate receptor 5 , levodopa , allosteric modulator , dyskinesia , pharmacology , metabotropic glutamate receptor , allosteric regulation , parkinsonism , glutamate receptor , parkinson's disease , neuroscience , medicine , psychology , receptor , disease
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