Effect of lesogaberan, a novel GABA(B)-receptor agonist, on transient lower oesophageal sphincter relaxations in male subjects

Aliment Pharmacol Ther. 2010 Jun;31(11):1208-17. doi: 10.1111/j.1365-2036.2010.04283.x. Epub 2010 Mar 4.


Background: Transient lower oesophageal sphincter relaxations (TLESRs) are a major mechanism behind gastro-oesophageal reflux disease (GERD).

Aim: To assess the effect of lesogaberan (AZD3355) - a novel peripherally active GABA(B) receptor agonist - on TLESRs.

Methods: Twenty-four healthy men were enrolled in this single-blind, placebo-controlled, randomized, single-centre, three-period crossover phase 1 study. Subjects were randomized to receive single oral doses of lesogaberan (0.8 mg/kg), baclofen (40 mg) and placebo, separated by washout periods of < or = 7 days. Subjects finished a meal 1 h after the dose. Oesophageal manometry and pH-metry measurements were taken during the 3 h after the meal.

Results: Twenty-one subjects completed the study. Compared with placebo, lesogaberan 0.8 mg/kg significantly reduced the number of TLESRs by 36% [geometric mean ratio (GMR): 0.64; 95% confidence interval (CI): 0.51-0.82] and significantly reduced the number of acid reflux episodes (mean reduction: 1.6; 95% CI: 0.34-2.9). Lesogaberan also significantly increased lower oesophageal sphincter (LES) pressure by 39% compared with placebo (GMR: 1.39; 95% CI: 1.18-1.64). Comparable results were observed with baclofen. Similar numbers of adverse events were reported by subjects taking lesogaberan and placebo.

Conclusion: Compared with placebo, lesogaberan significantly reduced TLESRs and acid reflux episodes and increased LES pressure.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Baclofen / administration & dosage*
  • Cross-Over Studies
  • Esophageal Sphincter, Lower / drug effects*
  • GABA Agonists / administration & dosage
  • GABA Agonists / pharmacokinetics
  • Gastroesophageal Reflux / drug therapy*
  • Humans
  • Male
  • Manometry
  • Middle Aged
  • Muscle Relaxation / drug effects*
  • Phosphinic Acids / administration & dosage*
  • Phosphinic Acids / pharmacokinetics
  • Propylamines / administration & dosage*
  • Propylamines / pharmacokinetics
  • Young Adult


  • GABA Agonists
  • Phosphinic Acids
  • Propylamines
  • lesogaberan
  • Baclofen