Novel therapeutics for gastro–esophageal reflux symptoms

Abstract

Approximately 20–30% of patients with gastro–esophageal reflux symptoms report inadequate symptom relief while on proton-pump inhibitor therapy. The mechanisms involved are failure of the antireflux barrier (transient lower esophageal sphincter relaxations), high proximal extent of the refluxate, esophageal hypersensitivity and impaired mucosal integrity. Persisting acid or nonacid reflux can be demonstrated in 40–50% of cases, suggesting that there is room for antireflux therapy in these patients. New antireflux compounds have been shown to decrease the occurrence of transient lower esophageal sphincter relaxations. The most promising classes of compounds are GABA type B agonists and metabotropic glutamate receptor 5 antagonists, which can reduce both reflux episodes and symptoms, but the development of these compounds has been abandoned for either safety issues or lack of efficacy. Esophageal hypersensitivity and impaired mucosal integrity may prove to be relevant therapeutic targets in the future.

Keywords::

• baclofen
• esophageal hypersensitivity
• GABA receptor
• gastro–esophageal reflux
• glutamate receptor
• pain modulators
• proton-pump inhibitor
• transient lower esophageal sphincter relaxation

Financial & competing interests disclosure

F Zerbib has served as a speaker, a consultant and an advisory board member for Addex Pharma SA, Xenoport, Shire-Movetis, Norgine, Sanofi Aventis, Astrazeneca, Janssen Cilag, Renckitt Benckiser, Abbott, Pfizer and Given Imaging. M Simon has no interests to declare. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.