Lesogaberan: GABA_B receptor agonist treatment of gastroesophageal reflux disease

(Chemical Equation Presented) Gastroesophageal reflux disease (GERD) is a highly prevalent medical disorder. Most patients require chronic medical therapy and proton pump inhibitors (PPIs) are the mainstay of treatment. Some patients, however, have persistent symptoms of reflux despite PPI therapy. A medication to treat the major pathophysiologic event that causes reflux, transient lower esophageal sphincter relaxations (TLESRs), could improve reflux symptoms and potentially reduce complications of persistent acid reflux. Baclofen, a GABA_B receptor agonist, has been shown to reduce TLESRs and acid reflux in both healthy volunteers and patients with GERD. Central nervous system (CNS) side effects limited its use in clinical practice. Lesogaberan is a novel, peripherally acting, GABA_B receptor agonist with limited CNS side effects that decreases TLESRs, reduces the number of acid reflux events and improves acid exposure time in the distal esophagus. This monograph will review the pharmacology, preclinical and clinical data, and discuss the safety of this new compound.