title: The mGluR5 negative allosteric modulator dipraglurant reduces dyskinesia in the MPTP macaque model.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Erwan
authors.initials: E
authors.lastname: Bezard
authors.forename: Elsa Y
authors.initials: EY
authors.lastname: Pioli
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.forename: Françoise
authors.initials: F
authors.lastname: Girard
authors.forename: Vincent
authors.initials: V
authors.lastname: Mutel
authors.forename: Charlotte
authors.initials: C
authors.lastname: Keywood
authors.forename: Francois
authors.initials: F
authors.lastname: Tison
authors.forename: Olivier
authors.initials: O
authors.lastname: Rascol
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Poli
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000097:blood / Q000188:drug therapy*; D018691:Excitatory Amino Acid Antagonists / Q000097:blood / Q000737:chemistry* / Q000627:therapeutic use*; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D007980:Levodopa / Q000009:adverse effects; D020267:MPTP Poisoning / Q000188:drug therapy*; D008253:Macaca mulatta; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D000978:Antiparkinson Agents; D018691:Excitatory Amino Acid Antagonists; D007093:Imidazoles; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D007980:Levodopa; C000596095:6-fluoro-2-(4-(pyridin-2-yl)but-3-yn-1-yl)imidazo(1,2-a)pyridine
keywords: MPTP; chorea; dystonia; macaque; on-time