Funding agencies: This study was supported by Addex Pharma SA.
The mGluR5 negative allosteric modulator dipraglurant reduces dyskinesia in the MPTP macaque model
Article first published online: 27 MAY 2014
© 2014 International Parkinson and Movement Disorder Society
Volume 29, Issue 8, pages 1074–1079, July 2014
How to Cite
Bezard, E., Pioli, E. Y., Li, Q., Girard, F., Mutel, V., Keywood, C., Tison, F., Rascol, O. and Poli, S. M. (2014), The mGluR5 negative allosteric modulator dipraglurant reduces dyskinesia in the MPTP macaque model. Mov. Disord., 29: 1074–1079. doi: 10.1002/mds.25920
Relevant conflicts of interest/financial disclosures: Nothing to report.
Full financial disclosures and author roles may be found in the online version of this article.
- Issue published online: 17 JUL 2014
- Article first published online: 27 MAY 2014
- Manuscript Accepted: 21 APR 2014
- Manuscript Revised: 8 APR 2014
- Manuscript Received: 13 JAN 2014
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.
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).
Dipraglurant inhibited dyskinesias in the LID macaque model, with best effect reached at 30 mg/kg dose with no alteration of levodopa efficacy.
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