Gastroprokinetic Effect of a New Benzamide Derivative Itopride and Its Action Mechanisms in Conscious Dogs

Abstract

ABSTRACT-The novel benzamide derivative itopride was assayed for its effect on gastrointestinal motility in conscious dogs when it was administered intraduodenally (i.d.). Gastrointestinal motility was measured by means of chronically implanted force transducers, and itopride at a dose of 10 mg/kg, i.d. or more in creased the gastric contractile force during the digestive state. Intraduodenal cisapride, domperidone and metoclopramide also stimulated gastric motility, and their threshold doses were 1, 3 and 1 mg/kg, respec tively. Dopamine infusion (1 mg/kg/hr, i.v.) caused the postprandial gastric motility to disappear, but it was immediately restored by itopride at a dose of 3 mg/kg, i.d. With itopride at 1 and 3 mg/kg, i.d., acetylcholine (0.05 mg/kg/min)-induced contractions were greatly enhanced. In addition to its gastric stimulation, itopride at doses of 10-100 mg/kg, p.o. inhibited apomorphine (0.1 mg/kg, s.c.)-induced vomiting in dogs. In conclusion, intraduodenal itopride stimulates gastric motility through both anti-dopa minergic and anti-acetylcholinesterase actions. Its gastroprokinetic threshold dose was as large as 3 10 times those of cisapride, domperidone and metoclopramide. These findings suggest that itopride is an orally active gastroprokinetic with a moderate anti-emetic action.

A comparative study of probiotic, prokinetic based triple therapy with USFDA regimen in the eradication of Helicobacter pylori in a tertiary care hospital

“…Itopride a novel gastro prokinetic agent stimulates gastrointestinal motor activity through dual mode of action antidopaminergic and anti-acetylcholinesterase actions and in addition it has an antiemetic action, accelerates gastric emptying and modulates gastric sensorimotor function. 14 In our study eradication rate was more with the group B in comparison to the group A (84% vs. 70%). The third Maastricht consensus report agreed that effective treatment for H.pylori should achieve an eradication rate over 80%.…”

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

“…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. In a recent meta-analysis, Hiyama et al (2007) reported that these gastroprokinetic agents are significantly more effective than placebo in the treatment of FD.…”

Applying Novel Nutrient Drink to Clinical Trial of Functional Dyspepsia

“…Administration of itopride 50 mg 3 times daily is used in standard practice. Itopride is thought to exert prokinetic effects by way of antidopaminergic and antiacetylcholinesterase actions 17 and probably to have effects on gastric accommodation and gastric hypersensitivity. The aims of the study were to develop a novel NDT protocol and investigate its potential for application to a clinical trial of FD.…”