Acotiamide improves stress‐induced impaired gastric accommodation

Ikeo, Koichi; Oshima, Tadayuki; Sei, Hiroo; Kondo, Takashi; Fukui, Hirokazu; Watari, Jiro; Miwa, Hiroto

doi:10.1111/nmo.12991

Cited by 18 publications

(17 citation statements)

References 49 publications

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“…Muscarinic receptors are present on smooth muscle cells as well as myenteric neurons in the wall of the stomach and are involved in the control of GI smooth muscle function . Recently, acotiamide, an antagonist of presynaptic muscarinic receptors, has been developed and approved in Japan for the treatment of FD . This first in class prokinetic agent inhibits acetylcholinesterase and antagonises the presynaptic M1 and M2 muscarinic receptors, present on cholinergic nerve endings, which leads to an increase in acetylcholine levels in the synaptic cleft .…”

Section: Current Treatment Options For Functional Dyspepsiamentioning

confidence: 99%

Review article: treatment options for functional dyspepsia

Masuy

Oudenhove

Tack

2019

Aliment Pharmacol Ther

100

124

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Background: Functional dyspepsia, consisting of epigastric pain syndrome and postprandial distress syndrome, is a prevalent functional gastrointestinal disorder. To date, only limited treatment options are available and conflicting results in terms of efficacy have been reported. Consequently, nonpharmacological treatment options are increasingly being explored for functional dyspepsia. Aim: To provide an overview of current pharmacological and nonpharmacological treatment options for functional dyspepsia. Methods: A literature search was conducted on Pubmed and other sources to identify relevant studies.Results: Acid suppressive therapy reduced symptoms in 30%-70% of the patients, with higher benefit in epigastric pain syndrome and superior effectiveness for proton pump inhibitors compared to H 2 -antagonists. Prokinetic agents, primarily used to treat postprandial distress syndrome, showed variable efficiency: 59%-81% responder rate for dopamine receptor antagonists, 32%-91% for serotonin-4-receptor agonists and 31%-80% for muscarinic receptor antagonists. H Pylori eradication, recommended in infected patients, was effective in 24%-82%. Refractory symptoms are addressed with neuromodulators. However, their efficacy in functional dyspepsia remains incompletely elucidated, available data showing symptom reduction in 27%-71% of the patients. Regarding herbal agents, peppermint oil reduced symptoms in 66%-91%, rikkunshito in 29%-34% and iberogast in 20%-95%. Lastly, acupuncture, cognitive behavioural therapy and hypnotherapy may help to provide symptom control, but research on their efficacy remains sparse.Conclusions: None of the available therapies is effective in the majority of patients without being associated with major side effects. Developing new treatment options is challenging due to the heterogeneity of functional dyspepsia, the lack of readily identified target mechanisms and the poor association between pathophysiological disturbances and symptoms.

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Section: Current Treatment Options For Functional Dyspepsiamentioning

confidence: 99%

Review article: treatment options for functional dyspepsia

Masuy

Oudenhove

Tack

2019

Aliment Pharmacol Ther

100

124

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“…Functional dyspepsia (FD) is a common disorder that is characterized by chronic or recurrent upper abdominal pain or discomfort without evidence of structural disease . Although the pathogenesis of FD remains largely unknown, various mechanisms such as genetic factors, impaired gastric motility, increased exposure of the duodenum to acid, visceral hypersensitivity, and altered brain‐gut duodenal axis interactions have been implicated . Low‐grade duodenal inflammation has recently been considered as a component of FD pathogenesis .…”

Section: Introductionmentioning

confidence: 99%

Duodenal low‐grade inflammation and expression of tight junction proteins in functional dyspepsia

Taki

Oshima

et al. 2019

Neurogastroenterology Motil

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Background Duodenal changes in functional dyspepsia (FD) might be related to the development of symptoms. However, relationships among low‐grade inflammation, Helicobacter pylori infection, and protein expression by tight junctions (TJs) in the duodenum are unclear. We therefore aimed to determine whether duodenal inflammation and genes associated with TJ proteins are associated with FD. Methods We evaluated inflammatory cell infiltration of the duodenum, H pylori infection, and genes associated with TJ proteins in duodenal biopsy specimens from 35 patients with FD according to the Rome III diagnostic questionnaire and from 31 asymptomatic controls without structural diseases. We immunohistochemically detected eosinophils and mast cells and counted them. The expression of claudins, occludin, and zonula occludens (ZO)‐1 mRNA was evaluated using quantitative RT‐PCR. Infection with H pylori was determined by measuring serum antibodies, rapid urease or urea breath tests, and endoscopic findings. Results Sex, age, and H pyloriinfection rates did not differ between patients with FD and controls. The numbers of eosinophils and mast cells were significantly increased in patients with FD compared with controls and were significantly correlated. Inflammatory cell counts in the duodenum were not associated with H pylori infection status. Claudin‐3 mRNA expression was increased in the patients with FD. Conclusions Subtle inflammation identified in the duodenum of patients with FD might be associated with the onset and persistence of dyspeptic symptoms.

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“…Acotiamide (Z-338), a new first-in-class prokinetic agent has been developed for the treatment of FD and has been approved in Japan in 2013. 13,14 It exerts its prokinetic function partly by inhibiting acetylcholinesterase (AChE) and by antagonizing the M1 and M2 muscarinic receptors, thereby decreasing the degradation and increasing the release of acetylcholine (Ach) from cholinergic enteric neurons. [14][15][16] Additionally, acotiamide may indirectly affect gastrointestinal functions by adjusting the activity of the braingut-axis.…”

Section: Introductionmentioning

confidence: 99%

Acotiamide affects antral motility, but has no effect on fundic motility, gastric emptying or symptom perception in healthy participants

Masuy

Tack

Verbeke

et al. 2019

Neurogastroenterology Motil

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Background Acotiamide, a prokinetic agent was shown to be efficacious in the treatment of functional dyspepsia (FD). The exact mechanism of action is incompletely elucidated. Methods This randomized, placebo‐controlled, cross‐over study aimed to examine the effect of acotiamide on gastric motility, measured as intragastric pressure, gastric emptying (GE) rate and gastrointestinal (GI) symptom perception in healthy volunteers (HVs). Participants were treated with acotiamide (100 mg tid) and placebo for 3 weeks, separated by a 1‐week washout period. A daily symptom diary was collected during both treatments. At the end of each treatment period, GE rate and gastric motility were assessed with a 13C‐octanoic acid breath test and high‐resolution manometry during nutrient infusion, respectively. GI symptom levels were scored during high‐resolution manometry. Data were analyzed using mixed models. The study was registered as NCT03402984. Key Results Twenty HVs (10 female, 25 ± 4.1 years, 22.58 ± 2.73 kg/m2) participated in the study. There was no difference in GE half time between both treatments (P = 0.92). Acotiamide had no effect on fundic pressures before and after nutrient infusion (P = 0.91). However, postprandial antral pressures remained significantly lower compared to placebo (P = 0.015). There was no significant difference in hunger, satiation and GI symptoms scores assessed during IGP measurement and by the daily diary (P > 0.12 for all). Conclusion Acotiamide is associated with lower antral pressures after nutrient intake, whereas it has no effect on fundic pressures, GE rate and symptom perceptions in HVs. Studies in FD need to elucidate whether lower antral pressures induced by acotiamide underlie postprandial symptom improvement in FD.

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Acotiamide improves stress‐induced impaired gastric accommodation

Abstract: Acotiamide prolongs gastric accommodation and improves stress-induced impaired gastric accommodation, indicating a potential role for acotiamide in the treatment of functional dyspepsia through its effects on gastric accommodation reactions.

Cited by 18 publications

References 49 publications

Review article: treatment options for functional dyspepsia

Review article: treatment options for functional dyspepsia

Duodenal low‐grade inflammation and expression of tight junction proteins in functional dyspepsia

Acotiamide affects antral motility, but has no effect on fundic motility, gastric emptying or symptom perception in healthy participants

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