Effect of EP1 Receptor Antagonist on Transient Lower Esophageal Sphincter Relaxations in Humans

• Published in: Digestion Vol. 101; no. 3; pp. 270 - 278
• Main Authors: Sawada, Akinari, Hashimoto, Atsushi, Uemura, Risa, Yamagami, Hirokazu, Tanigawa, Tetsuya, Watanabe, Toshio, Fujiwara, Yasuhiro
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.05.2020
• Subjects: Adult; Benzoates; Benzoates - administration & dosage; Cross-Over Studies; Double-Blind Method; Endoscopy, Digestive System; Endoscopy, Digestive System - methods; Esophageal Sphincter, Lower; Esophageal Sphincter, Lower - diagnostic imaging; Esophageal Sphincter, Lower - drug effects; Esophageal Sphincter, Lower - physiopathology; Female; Gastroesophageal Reflux; Gastroesophageal Reflux - physiopathology; Gastroesophageal Reflux - prevention & control; Humans; Indenes; Indenes - administration & dosage; Male; Manometry; Manometry - methods; Muscle Relaxation; Muscle Relaxation - drug effects; Muscle Relaxation - physiology; Postprandial Period; Receptors, Prostaglandin E, EP1 Subtype; Receptors, Prostaglandin E, EP1 Subtype - antagonists & inhibitors; Research Article; Thiazoles; Thiazoles - administration & dosage; Treatment Outcome; Young Adult; Esophageal motility; EP1 receptor; Gastroesophageal reflux disease; Lower esophageal sphincter
• ISSN: 0012-2823; 1421-9867; 1421-9867
• DOI: 10.1159/000499333

Background/Aims: Transient lower esophageal sphincter relaxations (TLESRs) are the major cause of gastroesophageal reflux. Recently, an EP1 receptor antagonist, ONO-8539, showed the reduction of TLESRs in monkeys. However, its effect on TLESRs in humans remains unclear. This study investigated the effect of ONO-8539 on postprandial TLESRs in healthy male subjects. Methods: Twenty-seven subjects participated in this placebo-controlled, cross-over study. The subjects received either placebo or ONO-8539 (450 mg) after a standardized breakfast. A 30-min basal recording was performed 4 h after drug administration. Subsequently, TLESR recordings were performed after a high-fat test meal for 3 h. The examination was repeated at least 7 days from the first evaluation for washout. Results: Thirteen patients were ultimately analyzed. The basal lower esophageal sphincter pressure was not different between the 2 groups (16.3 and 18.0 mm Hg for placebo and ONO-8539, respectively; p = 0.88). ONO-8539 significantly reduced the number of TLESRs from 15.0 to 12.0 for 3 h (p < 0.05). The proportion of terminating events of TLESRs was significantly different between the 2 groups (p < 0.05). No events and swallowing terminated more TLESRs with ONO-8539 than with placebo. Conclusions: ONO-8539 suppressed TLESRs mildly. EP1 receptor may be involved with the mechanism of human TLESRs.