GABAB receptors as drug targets to treat gastroesophageal reflux disease.
Article Details
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Lehmann A
GABAB receptors as drug targets to treat gastroesophageal reflux disease.
Pharmacol Ther. 2009 Jun;122(3):239-45. doi: 10.1016/j.pharmthera.2009.02.008. Epub 2009 Mar 19.
- PubMed ID
- 19303900 [ View in PubMed]
- Abstract
For many years, acid-suppressive therapy has been at the forefront of treating gastroesophageal reflux disease (GERD), yet despite the advent of the proton pump inhibitors (PPIs) some patients continue to experience persistent GERD symptoms. Therapeutic (non-surgical) options for such patients are currently limited. To tackle this clinical issue, research efforts have begun to focus on 'reflux inhibition' as a potential therapeutic target - i.e. inhibition of transient lower esophageal relaxations (TLESRs), the predominant mechanism of gastroesophageal reflux. Preclinical research has identified a number of drug targets through which TLESRs can be modulated, and the gamma-aminobutyric acid (GABA) type B (GABA(B)) receptor has emerged as one of the most promising. Studies with baclofen, a well-known agonist of this receptor, have demonstrated that reflux inhibition is a valid concept in the clinical setting in that reducing the incidence of TLESRs improves GERD symptoms. But baclofen is associated with significant central nervous system (CNS) side effects, rendering it undesirable for use as a treatment for GERD. Further development work has yielded a number of novel GABA(B) receptor agonists with reduced CNS side effect profiles, and clinical trials are currently being performed with several agents. Compounds that target TLESRs may therefore present a new add-on treatment for patients with persistent GERD symptoms despite PPI therapy.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Arbaclofen Gamma-aminobutyric acid type B receptor subunit 1 Protein Humans YesAgonistDetails Arbaclofen Gamma-aminobutyric acid type B receptor subunit 2 Protein Humans YesAgonistDetails Arbaclofen Placarbil Gamma-aminobutyric acid type B receptor subunit 1 Protein Humans YesAgonistDetails Arbaclofen Placarbil Gamma-aminobutyric acid type B receptor subunit 2 Protein Humans YesAgonistDetails Baclofen Gamma-aminobutyric acid type B receptor subunit 1 Protein Humans UnknownAgonistDetails Baclofen Gamma-aminobutyric acid type B receptor subunit 2 Protein Humans YesAgonistDetails