Control of transient lower oesophageal sphincter relaxations and reflux by the GABAB agonist baclofen in patients with gastro-oesophageal reflux disease

Background and aims: Transient lower oesophageal sphincter relaxations (TLOSRs) are the major cause of gastro-oesophageal reflux in normal subjects and in most patients with reflux disease, The gamma aminobutyric acid (GABA) receptor type B agonist, baclofen, is a potent inhibitor of TLOSRs in normal subjects. The aim of this study was to investigate the effect of baclofen on TLOSRs and postprandial gastro-oesophageal reflux in patients with reflux disease. Methods: In 20 patients with reflux disease, oesophageal motility and pH were measured, with patients in the sitting position, for three hours after a 3000 kJ mixed nutrient meal. On separate days of least one week apart, 40 mg oral baclofen or placebo was given 90 minutes before the meal. the rate of TLOSRs 40% (13.8-18.3) hours (p <0.0002) and basal lower oesophageal pressure. Baclofen also significantly reduced the rate of reflux episodes by 43% from 7.0 (4.0-12.0) to 4.0 (1.5-9) per three hours (median (interquartile range); p <0.02). However, baclofen had no effect on oesophageal acid exposure (baclofen 4.9% (1.7-12.4) v placebo 5.0% (2.7-15.5)). Conclusions: In patients with reflux disease, the GABA, agonist baclofen significantly inhibits gastrooesophageal reflux episodes by inhibition of TLOSRs. These findings suggest that GABA, agonists may be useful as therapeutic agents for the management of reflux disease.