02 Arbaclofen decrease.pdf

nature publishing group ORIGINAL CONTRIBUTIONS E S O P H A G U S 1 ? 2009 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY INTRODUCTION Gastroesophageal refl ux disease (GERD), characterized by symp- toms of heartburn and / or regurgitation, is common and increas- ing in prevalence. Population surveys in the United States have found that up to 44 % of adults suff er from heartburn at least once a month ( 1 ), 14 % at least weekly, and 7 % daily ( 2 ). An estimated 18 million patients with GERD in the United States receive pharmacological therapy with proton pump inhibi- tors (PPIs) or H 2 -blockers, the most commonly prescribed agents ( 3 ). PPIs eff ectively reduce refl uxate acidity by inhibition of the hydrogen / potassium adenosine triphosphatase enzyme system (H + / K + ATPase) of the gastric parietal cell. However, up to 40 % of patients with GERD fail to completely respond symptomati- cally to standard PPI doses ( 4 ). Moreover, refl ux episodes become predominantly nonacid aft er PPI treatment ( 5 ), and GERD symptoms are associated with nonacid, as well as acid, refl ux episodes ( 6 ). GERD is commonly associated with transient lower esophageal sphincter relaxations (TLESRs), which are relaxations not related to swallowing ( 7 ). TLESRs are triggered by gastric distension, mediated by mechanosensitive vagal aff erent neurons terminating in the brainstem, resulting in a vago-vagal refl ex motor pattern that also involves inhibition of the crural diaphragm and longitudinal muscle contractions in the distal esophagus ( 8,9 ). Racemic baclofen has been approved in the United States since 1977 to alleviate spasticity resulting from multiple sclerosis or spi- nal cord injury ( 10,11 ). Th e pharmacological activity of baclofen resides predominantly in the R-isomer, which is an agonist of the Arbaclofen Placarbil Decreases Postprandial Refl ux in Patients With Gastroesophageal Refl ux D