Lesogaberan, a GABA(B) agonist for the potential treatment of gastroesophageal reflux disease.
Lesogaberan, under development by AstraZeneca plc, is a GABA(B) agonist for the potential treatment of gastroesophageal reflux disease (GERD). In vitro, lesogaberan was an efficient GABA(B) agonist and was taken up by GABA(B) receptors, thereby maintaining low extracellular levels of lesogaberan in the CNS and avoiding the serious CNS side-effect profile of the GABA(B) agonist baclofen. In phase I and IIa clinical trials, lesogaberan treatment was well tolerated, and resulted in a substantial reduction in reflux episodes by decreasing the frequency of transient lower esophageal sphincter relaxations. At the time of publication, a phase IIa trial was ongoing in patients with GERD that was partially refractive to standard proton pump inhibitor (PPI) therapy. Lesogaberan may have potential to be used as an add-on therapy to PPIs. However, the safety, efficacy and advantages of lesogaberan compared with existing therapies remain to be established in phase IIb and III trials.
Bredenoord
Albert J
AJ
Saint Antonius Hospital, Department of Gastroenterology, PO Box 2500, 3430 EM Nieuwegein, The Netherlands. a.bredenoord@antonius.net
D000818:Animals; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004359:Drug Therapy, Combination; D049630:Esophageal Sphincter, Lower / Q000187:drug effects; D018755:GABA Agonists / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D058786:GABA-B Receptor Agonists; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D010721:Phosphinic Acids / Q000009:adverse effects / Q000494:pharmacology* / Q000633:toxicity; D011437:Propylamines / Q000009:adverse effects / Q000494:pharmacology* / Q000633:toxicity; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D018080:Receptors, GABA-B / Q000378:metabolism; D014018:Tissue Distribution
D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D010721:Phosphinic Acids; D011437:Propylamines; D054328:Proton Pump Inhibitors; D018080:Receptors, GABA-B; C545087:lesogaberan