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Control of transient lower esophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in normal subjects.
Gastroenterology. 2000 Jan; 118(1):7-13.G

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. 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.

Authors+Show Affiliations

Department of Gastrointestinal Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10611148

Citation

Lidums, I, et al. "Control of Transient Lower Esophageal Sphincter Relaxations and Reflux By the GABA(B) Agonist Baclofen in Normal Subjects." Gastroenterology, vol. 118, no. 1, 2000, pp. 7-13.
Lidums I, Lehmann A, Checklin H, et al. Control of transient lower esophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in normal subjects. Gastroenterology. 2000;118(1):7-13.
Lidums, I., Lehmann, A., Checklin, H., Dent, J., & Holloway, R. H. (2000). Control of transient lower esophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in normal subjects. Gastroenterology, 118(1), 7-13.
Lidums I, et al. Control of Transient Lower Esophageal Sphincter Relaxations and Reflux By the GABA(B) Agonist Baclofen in Normal Subjects. Gastroenterology. 2000;118(1):7-13. PubMed PMID: 10611148.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Control of transient lower esophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in normal subjects. AU - Lidums,I, AU - Lehmann,A, AU - Checklin,H, AU - Dent,J, AU - Holloway,R H, PY - 1999/12/28/pubmed PY - 1999/12/28/medline PY - 1999/12/28/entrez SP - 7 EP - 13 JF - Gastroenterology JO - Gastroenterology VL - 118 IS - 1 N2 - 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. 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. SN - 0016-5085 UR - https://www.unboundmedicine.com/medline/citation/10611148/Control_of_transient_lower_esophageal_sphincter_relaxations_and_reflux_by_the_GABA_B__agonist_baclofen_in_normal_subjects_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(00)70408-2 DB - PRIME DP - Unbound Medicine ER -