Control of transient lower esophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in normal subjects.
OBJECTIVE
Transient lower esophageal sphincter (LES) relaxations are the major mechanism of gastroesophageal reflux in normal subjects and in most patients with reflux disease. gamma-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 GABA(B) 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 GABA(B) agonist baclofen significantly inhibits gastroesophageal reflux by inhibition of transient LES relaxations. These findings suggest that GABA(B) agonists may be useful as therapeutic agents for the management of reflux in patients with gastroesophageal reflux disease.
Lidums
I
I
Department of Gastrointestinal Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
Lehmann
A
A
Checklin
H
H
Dent
J
J
Holloway
R H
RH
D000293:Adolescent; D000328:Adult; D001418:Baclofen / Q000009:adverse effects / Q000494:pharmacology*; D003679:Deglutition / Q000187:drug effects; D004311:Double-Blind Method; D004943:Esophagogastric Junction / Q000187:drug effects* / Q000502:physiology; D004947:Esophagus / Q000187:drug effects; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology*; D005764:Gastroesophageal Reflux / Q000188:drug therapy / Q000503:physiopathology; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D009125:Muscle Relaxants, Central / Q000009:adverse effects / Q000494:pharmacology*; D010528:Peristalsis / Q000187:drug effects; D011312:Pressure; D018709:Statistics, Nonparametric
D018755:GABA Agonists; D009125:Muscle Relaxants, Central; D019382:Human Growth Hormone; D001418:Baclofen