Novel Prokinetic Acotiamide Reduces Transient Lower Esophageal Sphincter Relaxation in Healthy Subjects

Abstract

Background/Aims: Currently, there is no study evaluating the effect of acotiamide on transient lower esophageal sphincter relaxations (TLESRs). The aim of this study was to evaluate the effect of acotiamide on TLESRs using simultaneous high-resolution manometry (HRM) and impedance-pH monitoring. Methods: Ten healthy subjects were enrolled. On day 1, subjects underwent HRM and impedance-pH recordings as a baseline. Subjects ate a 750-kcal liquid meal; recording was continued for 2 h while the subjects were in a sitting position. After the administration of acotiamide 100 mg three times a day for 1 week, subjects underwent HRM and impedance-pH recording under the same protocol. Results: A total of 208 TLESRs were identified at baseline. Acotiamide decreased the total number of TLESRs from 208 to 143 (p < 0.05). The rate of reflux events during TLESRs after acotiamide administration was similar to that at baseline (57% after acotiamide vs. 58% at baseline). Bolus clearance time was significantly reduced by acotiamide. Conclusions: Acotiamide was believed to have the potential for reducing TLESRs and for enhancing esophageal bolus clearance in healthy volunteers. Future research is needed to determine whether the effects of acotiamide that reduce TLESRs and enhance esophageal motility could improve symptoms in patients with refractory gastroesophageal reflux disease.

Effects of acotiamide on functional dyspepsia patients with heartburn who failed proton pump inhibitor treatment in Japanese patients: A randomized, double‐blind, placebo‐controlled crossover study

“…18 However, it has been reported that acotiamide has no apparent effect on esophageal movement in healthy people or GERD patients. 19,20 On the other hand, it has been reported that acotiamide reduced regurgitation with transient lower esophageal sphincter relaxation (TLESR) and improved esophageal clearance in healthy subjects, 38 and it ameliorated minor esophageal peristaltic abnormalities observed in healthy subjects. 39 In a recent report on acotiamide, Yamashita et al 40 Abbreviations: NS, not significant; SD, standard deviation.…”

“…The primary cause of GERD is thought to be esophageal motility dysfunction accompanied by weak esoph-ity and GERD has not been sufficiently investigated, and at present there is no consensus regarding these fields. On the other hand, it has been reported that acotiamide reduced regurgitation with transient lower esophageal sphincter relaxation (TLESR) and improved esophageal clearance in healthy subjects,38 and it ameliorated minor esophageal peristaltic abnormalities observed in healthy subjects 39. Acotiamide inhibits AChE, a catabolic enzyme of ACh, and also antagonizes muscarine M 1 and M 2 receptors, which exist on nerve endings.…”

Esophageal Motor Dysfunctions in Gastroesophageal Reflux Disease and Therapeutic Perspectives

“…It was observed that acotiamide can reduce TLESRs and enhancing esophageal bolus clearance in healthy subjects. 64 These observed effects would be favorable for treating patients with GERD and future research is needed.…”

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

“…Among them, TLESRs are considered to play a major role in provoking reflux [10]. Although several drugs, including γ-aminobutyric acid type B receptor agonists, histamine H2 receptor antagonists (nizatidine) [11], prokinetic agents (acotiamide [12], itopride [13]), atropine [14,15], and morphine [16], have been found to inhibit TLESRs in humans, these have not been used for GERD in clinical practice owing to their effects on the central nervous system or a lack of their efficacy in treating GERD. However, TLESRs are still an attractive target for the treatment of GERD.…”