Stimulatory mechanism of EM523-induced contractions in postprandial stomach of conscious dogs

Shiba, Yoshihiro; Mizumoto, Akiyoshi; Inatomi, Nobuhiro; Haga, Norihiro; Yamamoto, Osamu; Itoh, Zen

doi:10.1016/0016-5085(95)90638-x

Cited by 30 publications

(20 citation statements)

References 30 publications

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“…ϫ 1.0 mm i.d. Silascon Medical Grade Tubing; Kaneka Medics, Osaka, Japan) was placed in the vena cava superior through a branch vein of the right external jugular vein for the intravenous administration of drugs (Shiba et al, 1995). The lead wires of the transducers and the catheter were protected with a protective jacket.…”

Section: Methodsmentioning

confidence: 99%

“…In dogs in the digestive state, intravenous infusion of atropine at 0.05 mg/kg/h for 20 min was started immediately after a bolus injection at 0.05 mg/kg. This dose of atropine was confirmed to completely inhibit bethanechol-stimulated contraction in dogs (Shiba et al, 1995). Acotiamide at 1 mg/kg was then administered intravenously at 10 min after the start of atropine infusion.…”

mentioning

confidence: 87%

“…The cholingeric neuron is considered to be the major excitatory neuron involved in gastrointestinal motor activity, because most gastrointestinal contractions are strongly inhibited by atropine, a muscarinic receptor antagonist (Ormsbee and Mir, 1978;Shiba et al, 1995;Furuichi et al, 2001). Stimulation of peripheral dopamine D 2 receptors located on the postganglionic cholinergic nerves causes a decrease in ACh release from parasympathetic nerves (Takahashi et al, 1991).…”

Section: Gastroprokinetic Activity Of Acotiamide In Dogs 797mentioning

confidence: 99%

“…The cholingeric neuron is considered to be the major excitatory neuron involved in gastrointestinal motor activity, because most gastrointestinal contractions are strongly inhibited by atropine, a muscarinic receptor antagonist (Ormsbee and Mir, 1978;Shiba et al, 1995;Furuichi et al, 2001). Dopamine D 2 receptor antagonists (Brogden et al, 1982;Iwanaga et al, 1990Iwanaga et al, , 1996 and serotonin 5-HT 4 receptor agonists (Mine et al, 1997) are well known for their use as gastroprokinetic agents, and their ability to enhance gastrointestinal motility.…”

Section: Introductionmentioning

confidence: 99%

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Acotiamide Hydrochloride (Z-338), a New Selective Acetylcholinesterase Inhibitor, Enhances Gastric Motility without Prolonging QT Interval in Dogs: Comparison with Cisapride, Itopride, and Mosapride

Matsunaga¹,

Tanaka²,

Yoshinaga³

et al. 2010

J Pharmacol Exp Ther

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Acotiamide hydrochloride (acotiamide; N-[2-[bis(1-methylethyl) amino]ethyl]-2-[(2-hydroxy-4,5-dimethoxybenzoyl) amino] thiazole-4-carboxamide monohydrochloride trihydrate, Z-338) has been reported to improve meal-related symptoms of functional dyspepsia in clinical studies. Here, we examined the gastroprokinetic effects of acotiamide and its antiacetylcholinesterase activity as a possible mechanism of action in conscious dogs. Acotiamide increased postprandial gastric motor activity in conscious dogs with chronically implanted force transducers and, like itopride, mosapride, and cisapride, exhibited gastroprokinetic activity in these dogs. Furthermore, acotiamide improved clonidine-induced hypomotility and delayed gastric emptying. Acotiamide-enhanced postprandial gastroduodenal motility was suppressed completely by pretreatment with atropine, a muscarinic receptor antagonist. In in vitro studies, acotiamide enhanced acetylcholine-but not carbachol-induced contractile responses of guinea pig gastric antrum strips. Moreover, like itopride and neostigmine, acotiamide inhibited recombinant human and canine stomach-derived acetylcholinesterase (AChE) activity in vitro. The mode of the AChE inhibitory action of acotiamide was selective and reversible. Unlike itopride or mosapride, acotiamide showed no affinity for dopamine D 2 or serotonin 5-HT 4 receptors. With regard to cardiovascular side effects, unlike cisapride, acotiamide did not affect myocardial monophasic action potential duration, QT interval, or corrected QT interval in anesthetized dogs. These results suggest that acotiamide stimulates gastric motility in vivo by inhibiting AChE activity without affecting QT interval. Acotiamide thus represents a beneficial new drug for the treatment of functional dyspepsia involving gastric motility dysfunction, with differences from other prokinetic agents.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 87%

Section: Gastroprokinetic Activity Of Acotiamide In Dogs 797mentioning

confidence: 99%

“…The cholingeric neuron is considered to be the major excitatory neuron involved in gastrointestinal motor activity, because most gastrointestinal contractions are strongly inhibited by atropine, a muscarinic receptor antagonist (Ormsbee and Mir, 1978;Shiba et al, 1995;Furuichi et al, 2001). Dopamine D 2 receptor antagonists (Brogden et al, 1982;Iwanaga et al, 1990Iwanaga et al, , 1996 and serotonin 5-HT 4 receptor agonists (Mine et al, 1997) are well known for their use as gastroprokinetic agents, and their ability to enhance gastrointestinal motility.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Acotiamide Hydrochloride (Z-338), a New Selective Acetylcholinesterase Inhibitor, Enhances Gastric Motility without Prolonging QT Interval in Dogs: Comparison with Cisapride, Itopride, and Mosapride

Matsunaga¹,

Tanaka²,

Yoshinaga³

et al. 2010

J Pharmacol Exp Ther

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“…(Itoh et al, 1977 ;Itoh et al, 1978 ;Itoh et al, 1991 ;Mizumoto et al, 1993 ;Haga et al, 1996). In fact, these contractions were completely inhibited by atropine sulfate and partially inhibited by hexamethonium bromide (Qin et al, 1993 ;Shiba et al, 1995). Glucagon inhibited eryth romycin lactobionate-induced contractions only in the antrum (Fig.…”

Section: Discussionmentioning

confidence: 91%

Involvement of Cholinergic Motor Neurons in Pharmacological Regulation of Gastrointestinal Motility by Glucagon in Conscious Dogs.

Shimatani

1997

J. Smooth Muscle Res.

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To clarify the exact mechanisms of the pharmacological effects of glucagon on gastro intestinal motility, the following experiments were performed on the conscious and anesthe tized dogs. 1) During phase I of interdigestive migrating contractions (IMC) , glucagon (5 infusion for 5 minutes) induced phasic contractions in the duodenum , jejunum and ileum, but not in the antrum. These excitatory responses were also observed in the truncal vagotomized dogs. These contractions were abolished by atropine or hex amethonium in the conscious dogs, and also by tetrodotoxin in the anesthetized dogs . 2) Glucagon inhibited cisapride-induced contractions only in the antrum in the conscious dogs .After pre-treatment with hexamethonium, glucagon inhibited these contractions in the duodenum, jejunum and ileum as well as in the antrum. After pre-treatment with tetrodotoxin in the anesthetized dogs, glucagon did not affect acetylcholine-induced contrac tions in any region. 3) Glucagon inhibited spontaneous phase III contractions and eryth romycin-induced phase III-like contractions in the antrum, but did not inhibit either contrac tions in the other regions in the conscious dogs. These paradoxical effects of glucagon between the antrum and intestine were similar to those involved in the blockade of 5-hydroxytryptamine 3 receptors. After pre-treatment with hexamethonium , glucagon inhib ited these contractions in the duodenum, jejunum and ileum as well as in the antrum . In conclusion: 1) Glucagon latently inhibits cholinergic motor activities in the antrum and intestine not directly, by binding to either receptor on the smooth muscle cells , but through postganglionic cholinergic neurons and possibly through 5-hydroxytryptamine neurons. 2) On the other hand, in the intestine the reverse effects through preganglionic cholinergic neurons involving nicotinic and muscarinic receptors are more potent . 3) As a result, glucagon inhibits antral contractions and does not affect intestinal contractions in a con scious state.

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Intragastric administration of rikkunshito stimulates upper gastrointestinal motility and gastric emptying in conscious dogs

et al. 2012

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Stimulatory mechanism of EM523-induced contractions in postprandial stomach of conscious dogs

Cited by 30 publications

References 30 publications

Acotiamide Hydrochloride (Z-338), a New Selective Acetylcholinesterase Inhibitor, Enhances Gastric Motility without Prolonging QT Interval in Dogs: Comparison with Cisapride, Itopride, and Mosapride

Acotiamide Hydrochloride (Z-338), a New Selective Acetylcholinesterase Inhibitor, Enhances Gastric Motility without Prolonging QT Interval in Dogs: Comparison with Cisapride, Itopride, and Mosapride

Involvement of Cholinergic Motor Neurons in Pharmacological Regulation of Gastrointestinal Motility by Glucagon in Conscious Dogs.

Intragastric administration of rikkunshito stimulates upper gastrointestinal motility and gastric emptying in conscious dogs

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