Control of transient lower oesophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in patients with gastro-oesophageal reflux disease.
OBJECTIVE
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 at least one week apart, 40 mg oral baclofen or placebo was given 90 minutes before the meal.


RESULTS
Baclofen reduced the rate of TLOSRs by 40% from 15 (13.8-18.3) to 9 (5.8-13.3) per three hours (p<0.0002) and increased basal lower oesophageal sphincter 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(B) agonist baclofen significantly inhibits gastro-oesophageal reflux episodes by inhibition of TLOSRs. These findings suggest that GABA(B) agonists may be useful as therapeutic agents for the management of reflux disease.
Zhang
Q
Q
Department of Gastroenterology, Hepatology, and General Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
Lehmann
A
A
Rigda
R
R
Dent
J
J
Holloway
R H
RH
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001418:Baclofen / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004943:Esophagogastric Junction / Q000187:drug effects* / Q000502:physiology; D005260:Female; D018755:GABA Agonists / Q000627:therapeutic use*; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000503:physiopathology; D005769:Gastrointestinal Motility / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008297:Male; D008365:Manometry; D008875:Middle Aged; D018709:Statistics, Nonparametric
D018755:GABA Agonists; D001418:Baclofen