Premium
The selective metabotropic glutamate receptor 5 antagonist mavoglurant ( AFQ 056) reduces the incidence of reflux episodes in dogs and patients with moderate to severe gastroesophageal reflux disease
Author(s) -
RouzadeDominguez M.L.,
Pezous N.,
David O. J.,
Tutuian R.,
Bruley des Varannes S.,
Tack J.,
Malfertheiner P.,
Allescher H.D.,
Ufer M.,
Rühl A.
Publication year - 2017
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13058
Subject(s) - reflux , medicine , gastroenterology , gerd , placebo , prokinetic agent , antagonist , incidence (geometry) , anesthesia , disease , receptor , pathology , physics , alternative medicine , optics
Abstract Background Transient lower esophageal sphincter relaxations ( TLESR s) induced by gastric distension are modulated by the metabotropic glutamate receptor 5 ( mG luR5) that influences the vagal reflex loop. We therefore aimed to examine the effects of the selective mG luR5 antagonist mavoglurant ( AFQ 056) on the number of TLESR s in dogs and reflux episodes in patients with gastroesophageal reflux disease ( GERD ). Methods In a dog model, the number of meal‐induced TLESR s was determined after intravenous (0.03, 0.1, 0.3, and 1 mg kg −1 ) and oral (1, 3, and 10 mg kg −1 ) doses of mavoglurant with reference to vehicle. In a multicenter, randomized, double‐blind, placebo‐controlled, three‐period crossover study, the incidence of meal‐induced reflux episodes was assessed by esophageal impedance monitoring after single, oral doses of mavoglurant (50 and 400 mg) or baclofen (40 mg) in 30 patients with moderate to severe GERD . Key Results In dogs, mavoglurant reduced the number of TLESR s after intravenous and oral administration. In patients with GERD , the incidence of postprandial reflux episodes was significantly lower at a dose of 400 mg mavoglurant (−37.5% ; 90% confidence interval [ CI ]: −57.8, −17.2), whereas there was no significant difference at 50 mg of mavoglurant compared to placebo. A significantly lower incidence of reflux episodes was also noted with the active comparator baclofen (−50.3%; 90% CI : −66.2, −34.3), thereby validating this study. Conclusions and Inferences These data suggest a potential clinical benefit of mG luR5 antagonists such as mavoglurant in patients with GERD , particularly in those with persisting symptoms despite treatment with proton pump inhibitors.