Background and Aim: Acotiamide is a newly developed prokinetic drug that is clinically used to treat functional dyspepsia (FD). The objective of this study was to assess the therapeutic effects of acotiamide in patients with esophageal motility disorders (EMDs). Methods: Twenty-nine patients with both symptoms of FD and symptoms suspicious of EMDs were enrolled. Esophageal motility function was evaluated by high-resolution manometry before and after 2 weeks administration of acotiamide (100 mg) 3 times per day. Results: Twenty-nine patients were diagnosed with achalasia (n = 4), esophagogastric junction outflow obstruction (EGJOO) (n = 6), absent peristalsis (n = 2), distal esophageal spasm (n = 4), frequently failed peristalsis (n = 7), weak peristalsis (n = 2) and 4 of them were found to be normal. An analysis in all 29 patients showed that acotiamide had no effects on based on distal contractile integral (DCI), basal lower esophageal sphincter (LES) pressure, or integrated relaxation pressure (IRP). Subgroup analysis, however, showed that acotiamide dramatically reduced IRP, from 19.5 (15.1-30.8) to 12.1 (5.6-16.4) mm Hg, and DCI, from 2,517.9 (1,451.0-8,385.0) to 1,872.5 (812.3-5,225.3) mm Hg·cm·s, in the 6 patients with EGJOO. Conclusions: Acotiamide potentially normalized impaired LES relaxation in patients with EGJOO, while having no effects on normal esophageal motility patterns. Acotiamide may be a promising treatment for EGJOO.

Journal Section:
Original Paper
Keywords:
Esophageal motility disorder, Acotiamide, Esophagogastric junction outflow obstruction, High-resolution manometry
1.
Bredenoord AJ, Fox M, Kahrilas PJ, Pandolfino JE, Schwizer W, Smout AJ: Chicago classification criteria of esophageal motility disorders defined in high resolution esophageal pressure topography. Neurogastroenterol Motil 2012;24(suppl 1):57-65.
2.
Kahrilas PJ, Bredenoord AJ, Fox M, Gyawali CP, Roman S, Smout AJ, Pandolfino JE; International High Resolution Manometry Working Group: The Chicago classification of esophageal motility disorders, v3.0. Neurogastroenterol Motil 2015;27:160-174.
3.
Inoue H, Sato H, Ikeda H, Onimaru M, Sato C, Minami H, Yokomichi H, Kobayashi Y, Grimes KL, Kudo SE: Per-oral endoscopic myotomy: a series of 500 patients. J Am Coll Surg 2015;221:256-264.
4.
Allaix ME, Patti MG: Endoscopic dilatation, heller myotomy, and peroral endoscopic myotomy: treatment modalities for achalasia. Surg Clin North Am 2015;95:567-578.
5.
Vaezi MF, Richter JE: Diagnosis and management of achalasia. American college of gastroenterology practice parameter committee. Am J Gastroenterol 1999;94:3406-3412.
6.
Matsunaga Y, Tanaka T, Yoshinaga K, Ueki S, Hori Y, Eta R, Kawabata Y, Yoshii K, Yoshida K, Matsumura T, Furuta S, Takei M, Tack J, Itoh Z: Acotiamide hydrochloride (Z-338), a new selective acetylcholinesterase inhibitor, enhances gastric motility without prolonging qt interval in dogs: Comparison with cisapride, itopride, and mosapride. J Pharmacol Exp Ther 2011;336:791-800.
7.
Kawachi M, Matsunaga Y, Tanaka T, Hori Y, Ito K, Nagahama K, Ozaki T, Inoue N, Toda R, Yoshii K, Hirayama M, Kawabata Y, Takei M: Acotiamide hydrochloride (Z-338) enhances gastric motility and emptying by inhibiting acetylcholinesterase activity in rats. Eur J Pharmacol 2011;666:218-225.
8.
Matsueda K, Hongo M, Tack J, Saito Y, Kato H: A placebo-controlled trial of acotiamide for meal-related symptoms of functional dyspepsia. Gut 2012;61:821-828.
9.
Kusunoki H, Haruma K, Manabe N, Imamura H, Kamada T, Shiotani A, Hata J, Sugioka H, Saito Y, Kato H, Tack J: Therapeutic efficacy of acotiamide in patients with functional dyspepsia based on enhanced postprandial gastric accommodation and emptying: randomized controlled study evaluation by real-time ultrasonography. Neurogastroenterol Motil 2012;24:540-545, e250-e251.
10.
Ishimura N, Mori M, Mikami H, Shimura S, Uno G, Aimi M, Oshima N, Ishihara S, Kinoshita Y: Effects of acotiamide on esophageal motor function and gastroesophageal reflux in healthy volunteers. BMC Gastroenterol 2015;15:117.
11.
Kusano M, Shimoyama Y, Sugimoto S, Kawamura O, Maeda M, Minashi K, Kuribayashi S, Higuchi T, Zai H, Ino K, Horikoshi T, Sugiyama T, Toki M, Ohwada T, Mori M: Development and evaluation of FSSG: frequency scale for the symptoms of GERD. J Gastroenterol 2004;39:888-891.
12.
Bredenoord AJ, Hebbard GS: Technical aspects of clinical high-resolution manometry studies. Neurogastroenterol Motil 2012;24(suppl 1):5-10.
13.
Mittal RK, Chiareli C, Liu J, Shaker R: Characteristics of lower esophageal sphincter relaxation induced by pharyngeal stimulation with minute amounts of water. Gastroenterology 1996;111:378-384.
14.
Trifan A, Shaker R, Ren J, Mittal RK, Saeian K, Dua K, Kusano M: Inhibition of resting lower esophageal sphincter pressure by pharyngeal water stimulation in humans. Gastroenterology 1995;108:441-446.
15.
Clouse RE, Staiano A: Topography of the esophageal peristaltic pressure wave. Am J Physiol 1991;261(4 pt 1):G677-G684.
16.
Clouse RE, Staiano A, Alrakawi A: Development of a topographic analysis system for manometric studies in the gastrointestinal tract. Gastrointest Endosc 1998;48:395-401.
17.
Fox MR, Bredenoord AJ: Oesophageal high-resolution manometry: moving from research into clinical practice. Gut 2008;57:405-423.
18.
Pandolfino JE, Ghosh SK, Rice J, Clarke JO, Kwiatek MA, Kahrilas PJ: Classifying esophageal motility by pressure topography characteristics: a study of 400 patients and 75 controls. Am J Gastroenterol 2008;103:27-37.
19.
Tack J, Janssen P: Acotiamide (Z-338, YM443), a new drug for the treatment of functional dyspepsia. Expert Opin Investig Drugs 2011;20:701-712.
20.
Scherer JR, Kwiatek MA, Soper NJ, Pandolfino JE, Kahrilas PJ: Functional esophagogastric junction obstruction with intact peristalsis: a heterogeneous syndrome sometimes akin to achalasia. J Gastrointest Surg 2009;13:2219-2225.
21.
Kahrilas PJ, Boeckxstaens G: The spectrum of achalasia: lessons from studies of pathophysiology and high-resolution manometry. Gastroenterology 2013;145:954-965.
22.
Gyawali CP, Bredenoord AJ, Conklin JL, Fox M, Pandolfino JE, Peters JH, Roman S, Staiano A, Vaezi MF: Evaluation of esophageal motor function in clinical practice. Neurogastroenterol Motil 2013;25:99-133.
© 2016 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2016
You do not currently have access to this content.