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Eikichi Ihara, Kazumasa Muta, Keita Fukaura, Kazuhiko Nakamura
BACKGROUND: Based on Chicago Classification version 3.0, the disorders of esophagogastric junction outflow obstruction (EGJOO) include achalasia (types I, II and III) and EGJOO. Although no curative treatments are currently available for the treatment of the disorders of EGJOO, medical treatments, endoscopic pneumatic dilation (PD), laparoscopic Heller myotomy (LHM), and per-oral endoscopic myotomy (POEM) are usually the sought-after modes of treatment. Since the etiology and pathogenesis might vary depending on the types of EGJOO disorders, treatment strategies should be considered based on those subtypes...
2017: Digestion
Prinesh N Patel, Pradipbhai D Kalariya, Mohit Thummar, S Gananadhamu, R Srinivas
Acotiamide hydrochloride (ACT) is a drug used for the treatment of functional dyspepsia. Understanding which metabolites are likely to be formed in vivo is essential for interpreting pharmacology, pharmacokinetic and toxicology data. The metabolism of ACT has been investigated using a specific and sensitive liquid chromatography positive ion electrospray ionization high resolution tandem mass spectrometry (LC/ESI-HR-MS/MS) method. In vivo samples including rat plasma, urine and feces were collected separately after dosing healthy Sprague-Dawley (SD) rats at a dose of 20 mg kg (-1) ACT at different time points up to 24 h...
December 10, 2016: Biomedical Chromatography: BMC
Fermín Mearin, Enrique Rey, Agustín Balboa
This article discusses the most interesting presentations at Digestive Disease Week, held in San Diego, in the field of functional and motor gastrointestinal disorders. One of the most important contributions was undoubtedly the presentation of the new Rome IV diagnostic criteria for functional gastrointestinal disorders. We therefore devote some space in this article to explaining these new criteria in the most common functional disorders. In fact, there has already been discussion of data comparing Rome IV and Rome III criteria in the diagnosis of irritable bowel syndrome, confirming that the new criteria are somewhat more restrictive...
September 2016: Gastroenterología y Hepatología
K Ikeo, T Oshima, H Sei, T Kondo, H Fukui, J Watari, H Miwa
BACKGROUND: Gastric accommodation is a reflex reaction related to gastric reservoir function. Psychological stress, such as anxiety, inhibits gastric accommodation in humans. Acotiamide enhances the effect of acetylcholine in the enteric nervous system, enhances gastric contractility, and accelerates delayed gastric emptying. However, the effect of acotiamide on stress-induced impaired gastric accommodation remains unclear. Therefore, we examined the effect of acotiamide on gastric accommodation and stress-induced impaired gastric accommodation using a conscious guinea pig model...
November 14, 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Satoshi Shinozaki, Hiroyuki Osawa, Hirotsugu Sakamoto, Yoshikazu Hayashi, Alan Kawarai Lefor, Hironori Yamamoto
The effect of acotiamide on gastrointestinal symptoms is undefined. The aim of this study is to evaluate the effect of acotiamide on abdominal symptoms in patients with functional dyspepsia. We retrospectively reviewed 51 patients treated with acotiamide. We evaluated patient quality of life using the Izumo scale that detects changes in quality of life caused by abdominal symptoms. Acotiamide ameliorated the symptoms of functional dyspepsia at one and three months (improved: 61% vs 80%, p=0.029 and resolved: 17% vs 33%, p=0...
2016: Journal of Medical Investigation: JMI
Kumiko Nakamura, Toshihiko Tomita, Tadayuki Oshima, Haruki Asano, Takahisa Yamasaki, Takuya Okugawa, Takashi Kondo, Tomoaki Kono, Katsuyuki Tozawa, Yoshio Ohda, Hirokazu Fukui, Fukushima Kazuhito, Shozo Hirota, Jiro Watari, Hiroto Miwa
BACKGROUND: Acotiamide is widely used to improve symptoms in patients with functional dyspepsia (FD) in multiple large-scale clinical studies, but there are few reports about the drug's mechanism of action. The aim of this study was to assess the effects of acotiamide on gastric accommodation and gastric emptying, gastrointestinal symptoms, and health-related quality of life (HR-QOL) in a placebo-controlled study. METHODS: We conducted a randomized, double-blind placebo-controlled study...
September 17, 2016: Journal of Gastroenterology
Kazumasa Muta, Eikichi Ihara, Keita Fukaura, Osamu Tsuchida, Toshiaki Ochiai, Kazuhiko Nakamura
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...
2016: Digestion
Masahiro Ueda, Eisuke Iwasaki, Hidekazu Suzuki
Efficacy of acotiamide for improving symptoms in patients with functional dyspepsia was shown by several clinical trials. In a randomized, double-blind, placebo-controlled, parallel-group comparative Phase III trial conducted in Japan, 100 mg of acotiamide three times a day for 4 weeks was more effective than a placebo for improving symptoms, and quality of life. Acotiamide was well-tolerated treatment, with no significant adverse events. The aim of this review was to summarize the current evidence of the efficacy of acotiamide in the treatment of patients with functional dyspepsia...
2016: Clinical and Experimental Gastroenterology
Ryo Kato, Kiyokazu Nakajima, Tsuyoshi Takahashi, Yasuhiro Miyazaki, Tomoki Makino, Yukinori Kurokawa, Makoto Yamasaki, Shuji Takiguchi, Masaki Mori, Yuichiro Doki
The majority of systemic sclerosis (SSc) patients have gastrointestinal tract involvement, but therapies of prokinetic agents are usually unsatisfactory. Patients are often compromised by the use of steroid; therefore, a surgical indication including fundoplication has been controversial. There is no report that advanced SSc with severe gastroesophageal reflux disease (GERD) is successfully treated with acotiamide, which is the acetylcholinesterase (AChE) inhibitor designed for functional dyspepsia (FD). We report a 44-year-old woman of SSc with severe GERD successfully treated with acotiamide...
December 2016: Surgical Case Reports
Jiawei He, Xianglin Ma, Qing Wang, Yanmei Huang, Hui Li
The interaction between acotiamide hydrochloride and pepsin was systematically characterized by fluorescence and electrochemical approaches. Fluorescence lifetime measurements showed that acotiamide hydrochloride quenched the intrinsic fluorescence of pepsin with a new complex formation via static mode, which was reconfirmed by cyclic voltammetry results. Both of the binding number and binding constants were calculated from differential pulse voltammetry analysis and fluorescence spectroscopy. The values obtained from the above two methods displayed a relatively high degree of consistency...
July 2016: Journal of Biochemical and Molecular Toxicology
Jing Li, Rui Huang, Zhi Wang, Haijun Qu, Meijuan Sun, Zhenhuan Zhao
Acotiamide is a new prokinetic drug that is used to treat functional dyspepsia (FD). A sensitive and specific LC-MS-MS method has been developed and validated for the analysis of acotiamide in rat plasma. The assay involved a simple protein precipitation (PPT) step with methanol-acetonitrile (50:50, v/v) and a gradient elution using a mobile phase consisting of water containing 0.1% formic acid and methanol containing 0.1% formic acid. The analytes were chromatographed on a reverse-phase Agilent Zorbax XDB C18 column (2...
July 2016: Journal of Chromatographic Science
H Yamawaki, S Futagami, T Kawagoe, Y Maruki, S Hashimoto, H Nagoya, H Sato, Y Kodaka, K Gudis, T Akamizu, C Sakamoto, K Iwakiri
BACKGROUND: The aim of this study is to clarify whether acotiamide and rabeprazole combination therapy can improve clinical symptoms, gastric emptying, and satisfaction with treatment in functional dyspepsia (FD) patients more effectively than acotiamide or rabeprazole monotherapy alone. We also aimed to determine whether acotiamide affects these changes via its effect on gastric emptying and appetite-related hormones such as ghrelin. METHODS: We used Rome III criteria to evaluate upper abdominal symptoms and anxiety by the State-Trait Anxiety Inventory (STAI)...
July 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Kate Napthali, Natasha Koloski, Marjorie M Walker, Nicholas J Talley
Functional dyspepsia is relatively common yet poorly understood. The best accepted diagnostic criteria are the Rome III criteria. The epidemiology, healthcare seeking rates, impact and pathophysiology are reviewed with a focus on women. Treatment is limited with no clearly established regimen currently recommended. Duodenal eosinophilia may be found in a subset. Proton pump inhibitors and prokinetic agents represent the standard therapeutic regimen after Helicobacter pylori infection has been eliminated. Some novel agents such as the prokinetic acotiamide appear promising; however, the need for a safe and efficacious treatment remains largely unmet...
2016: Women's Health
M Matsushita, T Masaoka, H Suzuki
BACKGROUND: Acotiamide hydrochloride (Z-338) is a new therapeutic agent for functional dyspepsia (FD). In 2013, the use of acotiamide was approved by the Japanese health insurance system. PURPOSE: The aim of this review is to summarize the present staus of basic and clinical approach to acotiamide for the treatment of functional dyspepsia. The agent inhibits acetylcholinesterase in vitro and enhances muscle motility ex vivo. In phase-II studies, 100 mg three times daily (t...
May 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Kazuyoshi Yoshii, Takashi Yamaguchi, Masamichi Hirayama, Ryoko Toda, Toshiko Kinomoto, Yoshihiro Kawabata, Kan Chiba
AIMS: Acotiamide is the first-in-class drug for the treatment of functional dyspepsia. Although pharmacological and therapeutic actions of acotiamide are thought to be derived from its inhibitory effects on acetylcholinesterase (AChE), whether the concentration of acotiamide at the site of action is sufficient to inhibit AChE remains unclear. Since major site of acotiamide action is thought to be the cholinergic nerve terminals in gastric myenteric plexus, we studied the distribution of [(14)C]acotiamide into gastric myenteric plexus...
January 15, 2016: Life Sciences
K Ito, M Kawachi, Y Matsunaga, Y Hori, T Ozaki, K Nagahama, M Hirayama, Y Kawabata, Y Shiraishi, M Takei, T Tanaka
Acotiamide is a first-in-class prokinetic drug approved in Japan for the treatment of functional dyspepsia. Given that acotiamide enhances gastric motility in conscious dogs and rats, we assessed the in vitro effects of this drug on the contraction of guinea pig stomach strips and on acetylcholinesterase (AChE) activity in stomach homogenate following fundus removal. We also investigated the serotonin 5-HT4 receptor agonist mosapride, dopamine D2 receptor and AChE inhibitor itopride, and representative AChE inhibitor neostigmine...
April 2016: Drug Research
Norihisa Ishimura, Mami Mori, Hironobu Mikami, Shino Shimura, Goichi Uno, Masahito Aimi, Naoki Oshima, Shunji Ishihara, Yoshikazu Kinoshita
BACKGROUND: The prevalence of gastroesophageal reflux disease (GERD) has been increasing worldwide, with proton pump inhibitor (PPI) administration the current mainstay therapy for affected individuals. However, PPI efficacy is insufficient especially for non-erosive reflux disease. Although it has been reported that prokinetic drugs improve GERD, their effects on esophageal function remain to be clearly investigated. In the present study, we evaluated the direct effects of acotiamide, a novel prokinetic agent for the treatment of functional dyspepsia, on esophageal motor function and gastroesophageal reflux...
September 11, 2015: BMC Gastroenterology
Kazuyoshi Yoshii, Minami Iikura, Masamichi Hirayama, Ryoko Toda, Yoshihiro Kawabata
PURPOSE: Acotiamide, a gastroprokinetic agent used to treat functional dyspepsia, is transported to at least two compartments in rat stomach. However, the role of these stomach compartments in pharmacokinetics and pharmacodynamics of acotiamide remains unclear. Thus, the purpose of this study was to elucidate the relationship of the blood and stomach concentration of acotiamide with its inhibitory effect on acetylcholinesterase (AChE). METHODS: Concentration profiles of acotiamide and acetylcholine (ACh) were determined after intravenous administration to rats and analyzed by physiologically-based pharmacokinetic and pharmacodynamic (PBPK/PD) model containing vascular space, precursor pool and deep pool of stomach...
February 2016: Pharmaceutical Research
Hiroshi Yamashita, Atsushi Kanamori, Takumi Fukuchi, Masahiro Tsujimae, Akio Koizumi, Taro Iwatsubo, Shintaro Koyama, Takaaki Eguchi, Satoshi Ubukata, Mikio Fujita, Akihiko Okada
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...
2015: Digestion
Mariko Hojo, Akihito Nagahara, Daisuke Asaoka, Sumio Watanabe
Functional dyspepsia (FD) is a multifactorial disease with complex underlying pathophysiology. To date, there is no established treatment for FD. This review summarizes recent progress in pharmacological therapy for the disease. A newly developed drug, acotiamide, is expected to improve symptoms of postprandial distress syndrome. Herbal medicines are also expected to become options for FD treatment.
October 2013: Clinical Journal of Gastroenterology
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