The effects of a novel metabotropic glutamate receptor 5 antagonist (AZD2066) on transient lower oesophageal sphincter relaxations and reflux episodes in healthy volunteers

Aliment Pharmacol Ther. 2012 May;35(10):1231-42. doi: 10.1111/j.1365-2036.2012.05081.x. Epub 2012 Apr 2.


Background: Selective metabotropic glutamate receptor 5 (mGluR5) antagonists inhibit transient lower oesophageal sphincter relaxations (TLESRs) in animals and acid reflux in humans.

Aim: To assess the effect of single doses of the mGluR5 antagonist AZD2066 on TLESRs and reflux in humans.

Methods: Healthy male volunteers received AZD2066 13 mg and placebo (part A), or AZD2066 2 mg and AZD2066 6 mg and placebo (part B), in a randomised crossover study. Postprandial manometry/pH-impedance measurements were taken after each dose.

Results: A total of 13 individuals completed part A of the study and 19 individuals completed part B. There was a significant reduction in the geometric mean number of TLESRs (27%; P = 0.02) and the geometric mean number of reflux episodes (51%; P = 0.01) in subjects receiving AZD2066 13 mg compared with placebo. Adverse events in participants receiving AZD2066 13 mg were mostly related to the nervous system [dizziness (3/13); disturbance in attention (3/13)]. Adverse events were reversible and of mild intensity. There were no serious adverse events. The effects of AZD2066 appeared dose-dependent, with smaller reductions in TLESRs and reflux episodes (relative to placebo) and fewer adverse events observed for AZD2066 2 mg and AZD2066 6 mg compared with AZD2066 13 mg.

Conclusion: The mGluR5-mediated inhibition of TLESRs may be a useful approach for inhibiting gastro-oesophageal reflux.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Esophageal Sphincter, Lower / drug effects*
  • Gastroesophageal Reflux / drug therapy*
  • Gastrointestinal Agents / administration & dosage*
  • Gastrointestinal Agents / pharmacokinetics
  • Gastrointestinal Agents / pharmacology
  • Humans
  • Hydrogen-Ion Concentration
  • Isoxazoles / administration & dosage*
  • Isoxazoles / pharmacokinetics
  • Isoxazoles / pharmacology
  • Male
  • Postprandial Period / drug effects
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / administration & dosage
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Triazoles / administration & dosage*
  • Triazoles / pharmacokinetics
  • Triazoles / pharmacology
  • Young Adult


  • AZD2066
  • GRM5 protein, human
  • Gastrointestinal Agents
  • Isoxazoles
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Triazoles