Gastroenterology

Gastroenterology

Volume 118, Issue 1, January 2000, Pages 7-13
Gastroenterology

Alimentary Tract
Control of transient lower esophageal sphincter relaxations and reflux by the GABAB agonist baclofen in normal subjects

https://doi.org/10.1016/S0016-5085(00)70408-2Get rights and content

Abstract

Background & Aims: Transient lower esophageal sphincter (LES) relaxations are the major mechanism of gastroesophageal reflux in normal subjects and in most patients with reflux disease. γ-Aminobutyric acid (GABA) is an important inhibitory neurotransmitter within the central nervous system which is present in regions of the brainstem that are believed to mediate transient LES relaxations. The aim of this study was to investigate the effect of a GABAB agonist baclofen on postprandial gastroesophageal reflux and transient LES relaxations. Methods: In 20 healthy volunteers, esophageal motility and pH were measured, with the subjects in the sitting position, for 3 hours after a 3000-kJ mixed nutrient meal. On separate days at least 1 week apart, 40 mg oral baclofen or placebo was given 90 minutes before the meal. Results: Baclofen significantly reduced the rate of reflux episodes by more than 60% from 1.0 (0.3-2.7) to 0.3 (0-1.0) per hour (median [interquartile range]). Baclofen also reduced the rate of transient LES relaxations from 5.7 (4.9-7.8) to 2.2 (1.3-3.8) per hour and increased basal LES pressure from 8.7 ± 1.4 to 10.8 ± 0.8 mm Hg. Conclusions: In normal human subjects, the GABAB agonist baclofen significantly inhibits gastroesophageal reflux by inhibition of transient LES relaxations. These findings suggest that GABAB agonists may be useful as therapeutic agents for the management of reflux in patients with gastroesophageal reflux disease.

GASTROENTEROLOGY 2000;118:7-13

Section snippets

Subjects

Studies were performed in 20 healthy subjects (14 men and 6 women) aged 18-39 years (median, 24 years) with a mean (±SEM) weight of 72 ± 2 kg. Subjects had no gastrointestinal symptoms, no history of upper gastrointestinal surgery, or no family history of epilepsy and were not taking regular antacids or medications known to influence esophageal motor function. Each subject gave written informed consent, and the protocol was approved by the Research Ethics Committee of the Royal Adelaide

Results

Data on esophageal pH were available in only 17 subjects because of technical problems with the pH recording system on at least 1 of the study days in 3 subjects.

Discussion

Current pharmacological treatment of reflux disease is based on acid suppression or prokinetic agents, or both. These approaches do not address the major mechanism underlying reflux of gastric contents into the esophagus, transient LES relaxation, which is clearly the most prevalent mechanism in most patients with reflux disease, particularly those with either no mucosal breaks or with only mild erosive esophagitis who comprise the bulk of patients with reflux disease. Therefore, control of

Acknowledgements

The authors thank Dr. M. Flardh for performing the baclofen assays.

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    Supported by a project grant from Astra Hässle AB (Mölndal, Sweden). Dr. Lidums was supported by a Dawes Scholarship from the Royal Adelaide Hospital.

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