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.

1.
Fass R: Therapeutic options for refractory gastroesophageal reflux disease. J Gastroenterol Hepatol 2012;27(suppl 3):3-7.
[PubMed]
2.
Vela MF, Camacho-Lobato L, Srinivasan R, Tutuian R, Katz PO, Castell DO: Simultaneous intraesophageal impedance and pH measurement of acid and nonacid gastroesophageal reflux: effect of omeprazole. Gastroenterology 2001;120:1599-1606.
[PubMed]
3.
Frazzoni M, Conigliaro R, Melotti G: Weakly acidic refluxes have a major role in the pathogenesis of proton pump inhibitor-resistant reflux oesophagitis. Aliment Pharmacol Ther 2011;33:601-606.
[PubMed]
4.
Tsoukali E, Sifrim D: The role of weakly acidic reflux in proton pump inhibitor failure, has dust settled? J Neurogastroenterol Motil 2010;16:258-264.
[PubMed]
5.
Piessevaux H, Tack J, Wilmer A, Coulie B, Geubel A, Janssens J: Perception of changes in wall tension of the proximal stomach in humans. Gut 2001;49:203-208.
[PubMed]
6.
Mainie I, Tutuian R, Agrawal A, Adams D, Castell DO: Combined multichannel intraluminal impedance-pH monitoring to select patients with persistent gastro-oesophageal reflux for laparoscopic Nissen fundoplication. Br J Surg 2006;93:1483-1487.
[PubMed]
7.
Vela MF, Tutuian R, Katz PO, Castell DO: Baclofen decreases acid and non-acid post-prandial gastro-oesophageal reflux measured by combined multichannel intraluminal impedance and pH. Aliment Pharmacol Ther 2003;17:243-251.
[PubMed]
8.
McCallum RW, Berkowitz DM, Lerner E: Gastric emptying in patients with gastroesophageal reflux. Gastroenterology 1981;80:285-291.
[PubMed]
9.
Cunningham KM, Horowitz M, Riddell PS, Maddern GJ, Myers JC, Holloway RH, Wishart JM, Jamieson GG: Relations among autonomic nerve dysfunction, oesophageal motility, and gastric emptying in gastro-oesophageal reflux disease. Gut 1991;32:1436-1440.
[PubMed]
10.
Pauwels A, Altan E, Tack J: The gastric accommodation response to meal intake determines the occurrence of transient lower esophageal sphincter relaxations and reflux events in patients with gastro-esophageal reflux disease. Neurogastroenterol Motil 2014;26:581-588.
[PubMed]
11.
Ogishima M, Kaibara M, Ueki S, Kurimoto T, Taniyama K: Z-338 facilitates acetylcholine release from enteric neurons due to blockade of muscarinic autoreceptors in guinea pig stomach. J Pharmacol Exp Ther 2000;294:33-37.
[PubMed]
12.
Nakajima T, Nawata H, Ito Y: Z-338, a newly synthetized carboxyamide derivative, stimulates gastric motility through enhancing the excitatory neurotransmission. J Smooth Muscle Res 2000;36:69-81.
[PubMed]
13.
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.
[PubMed]
14.
Kuribayashi S, Iwakiri K, Kawada A, Kawami N, Hoshino S, Takenouchi N, Hosaka H, Shimoyama Y, Kawamura O, Yamada M, Kusano M: Variant parameter values-as defined by the Chicago criteria-produced by ManoScan and a new system with Unisensor catheter. Neurogastroenterol Motil 2015;27:188-194.
[PubMed]
15.
Roman S, Zerbib F, Belhocine K, des Varannes SB, Mion F: High resolution manometry to detect transient lower oesophageal sphincter relaxations: diagnostic accuracy compared with perfused-sleeve manometry, and the definition of new detection criteria. Aliment Pharmacol Ther 2011;34:384-393.
[PubMed]
16.
Kuribayashi S, Massey BT, Hafeezullah M, Perera L, Hussaini SQ, Tatro L, Darling RJ, Franco R, Shaker R: Terminating motor events for TLESR are influenced by the presence and distribution of refluxate. Am J Physiol Gastrointest Liver Physiol 2009;297:G71-G75.
[PubMed]
17.
Bredenoord AJ, Weusten BL, Timmer R, Akkermans LM, Smout AJ: Relationships between air swallowing, intragastric air, belching and gastro-oesophageal reflux. Neurogastroenterol Motil 2005;17:341-347.
[PubMed]
18.
Holloway RH, Hongo M, Berger K, McCallum RW: Gastric distention: a mechanism for postprandial gastroesophageal reflux. Gastroenterology 1985;89:779-784.
[PubMed]
19.
Holloway RH, Kocyan P, Dent J: Provocation of transient lower esophageal sphincter relaxations by meals in patients with symptomatic gastroesophageal reflux. Dig Dis Sci 1991;36:1034-1039.
[PubMed]
20.
Richter J: Do we know the cause of reflux disease? Eur J Gastroenterol Hepatol 1999;11(suppl 1):S3-S9.
[PubMed]
21.
Ribolsi M, Holloway RH, Emerenziani S, Balestrieri P, Cicala M: Impedance-high resolution manometry analysis of patients with nonerosive reflux disease. Clin Gastroenterol Hepatol 2014;12:52-57.
[PubMed]
22.
Kahrilas PJ: GERD pathogenesis, pathophysiology, and clinical manifestations. Cleve Clin J Med 2003;70(suppl 5):S4-S19.
[PubMed]
23.
Rohof WO, Boeckxstaens GE, Hirsch DP: High-resolution esophageal pressure topography is superior to conventional sleeve manometry for the detection of transient lower esophageal sphincter relaxations associated with a reflux event. Neurogastroenterol Motil 2011;23:427-432.e173.
[PubMed]
24.
Zai H, Matsueda K, Kusano M, Urita Y, Saito Y, Kato H: Effect of acotiamide on gastric emptying in healthy adult humans. Eur J Clin Invest 2014;44:1215-1221.
[PubMed]
25.
Castell DO, Murray JA, Tutuian R, Orlando RC, Arnold R: Review article: the pathophysiology of gastro-oesophageal reflux disease - oesophageal manifestations. Aliment Pharmacol Ther 2004;20(suppl 9):14-25.
[PubMed]
26.
Zerbib F, Duriez A, Roman S, Capdepont M, Mion F: Determinants of gastro-oesophageal reflux perception in patients with persistent symptoms despite proton pump inhibitors. Gut 2008;57:156-160.
[PubMed]
27.
Emerenziani S, Ribolsi M, Sifrim D, Blondeau K, Cicala M: Regional oesophageal sensitivity to acid and weakly acidic reflux in patients with non-erosive reflux disease. Neurogastroenterol Motil 2009;21:253-258.
[PubMed]
28.
Emerenziani S, Sifrim D, Habib FI, Ribolsi M, Guarino MP, Rizzi M, Caviglia R, Petitti T, Cicala M: Presence of gas in the refluxate enhances reflux perception in non-erosive patients with physiological acid exposure of the oesophagus. Gut 2008;57:443-447.
[PubMed]
29.
Yamashita H, Ashida K, Fukuchi T, Nagatani Y, Koga H, Senda K, Eguchi T, Ubukata S, Kawaguchi S, Ueda A, Tanaka T, Ohashi R, Ito D, et al: Combined pH-impedance monitoring and high-resolution manometry of Japanese patients treated with proton-pump inhibitors for persistent symptoms of non-erosive reflux disease. J Smooth Muscle Res 2012;48:125-135.
[PubMed]
30.
Tack J, Zerbib F, Blondeau K, Des Varannes SB, Piessevaux H, Borovicka J, Mion F, Fox M, Bredenoord AJ, Louis H, Dedrie S, Hoppenbrouwers M, Meulemans A, Rykx A, Thielemans L, Ruth M: Randomized clinical trial: effect of the 5-HT4 receptor agonist revexepride on reflux parameters in patients with persistent reflux symptoms despite PPI treatment. Neurogastroenterol Motil 2015;27:258-268.
[PubMed]
31.
Helm JF, Dodds WJ, Pelc LR, Palmer DW, Hogan WJ, Teeter BC: Effect of esophageal emptying and saliva on clearance of acid from the esophagus. N Engl J Med 1984;310:284-288.
[PubMed]
32.
Nagahama K, Matsunaga Y, Kawachi M, Ito K, Tanaka T, Hori Y, Oka H, Takei M: Acotiamide, a new orally active acetylcholinesterase inhibitor, stimulates gastrointestinal motor activity in conscious dogs. Neurogastroenterol Motil 2012;24:566-574.e256.
[PubMed]
You do not currently have access to this content.