mavoglurant and Gastroesophageal-Reflux

Transient lower esophageal sphincter relaxations (TLESRs) induced by gastric distension are modulated by the metabotropic glutamate receptor 5 (mGluR5) that influences the vagal reflex loop. We therefore aimed to examine the effects of the selective mGluR5 antagonist mavoglurant (AFQ056) on the number of TLESRs in dogs and reflux episodes in patients with gastroesophageal reflux disease (GERD).. In a dog model, the number of meal-induced TLESRs was determined after intravenous (0.03, 0.1, 0.3, and 1 mg kg. In dogs, mavoglurant reduced the number of TLESRs 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.. These data suggest a potential clinical benefit of mGluR5 antagonists such as mavoglurant in patients with GERD, particularly in those with persisting symptoms despite treatment with proton pump inhibitors.

Topics: Administration, Intravenous; Administration, Oral; Adolescent; Adult; Aged; Animals; Dogs; Double-Blind Method; Esophageal Sphincter, Lower; Female; Gastroesophageal Reflux; Humans; Incidence; Indoles; Male; Middle Aged; Postprandial Period; Receptor, Metabotropic Glutamate 5; Treatment Outcome; Young Adult