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| Trade names | Ganaton |
| AHFS/Drugs.com | International Drug Names |
| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Bioavailability | ~60% (Tmax = 35±5 min) |
| Protein binding | 96% |
| Metabolism | Extensive hepatic (FMO1 andFMO3), primarilyN-oxidation[2] |
| Eliminationhalf-life | 5.7±0.3 hours |
| Excretion | Renal (3.7–4.1% as unchanged itopride, 75.4–89.4% as itopride-N-oxide)[1] |
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| ECHA InfoCard | 100.222.888 |
| Chemical and physical data | |
| Formula | C20H26N2O4 |
| Molar mass | 358.438 g·mol−1 |
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Itopride (INN; brand nameGanaton) is aprokineticbenzamide derivative. These drugs inhibitdopamine and acetylcholine esterase enzyme and have agastrokinetic effect.[3] Itopride is indicated for the treatment offunctional dyspepsia and other gastrointestinal conditions.[4] It is a combinedD2 receptorantagonist andacetylcholinesterase inhibitor.[5][6] Itopride is the dimethoxy analog oftrimethobenzamide.
Typically, itopride is indicated in the treatment of GI symptoms caused by reduced GI motility:
Itopride was shown to significantly improve symptoms in patients with functional dyspepsia and motility disorders in placebo-controlled trials.
These studies concluded that the reduction in the severity of symptoms offunctional dyspepsia after 8 weeks of treatment with itopride indicated that itopride was significantly superior to placebo and that itopride yielded a greater rate of response than placebo in significantly reducing pain and fullness.[4]
Central nervous system adverse effects do not tend to occur due to poor penetration across the blood brain barrier, although a slight raising of prolactin levels may occur.[7] Raising of prolactin levels is more common with high dose regimes of itopride.[11]
Itopride belongs to the samebenzamide group ascisapride, a drug found to affectQT interval and possibly predispose those using it to cardiacarrhythmias. However, itopride does not have any adverse effect on the QT interval.[7]
Later, in a study conducted with healthy adult volunteers, itopride was shown as unlikely to cause cardiac arrhythmias or ECG changes in part to the lack of significant interaction and metabolism via thecytochrome P450 enzyme pathway, unlikecisapride andmosapride, as it is metabolized by a different enzyme set. New molecular studies on guinea pig ventricularmyocytes also supported the cardiac safety profile of itopride, as it did not affect certain potassium mechanisms that may have been affected by cisapride or mosapride. Moreover, itopride has no affinity for the5-HT4 receptors, unlike otherbenzamides such as cisapride and mosapride, which are 5-HT4 agonists. The affinity of cisapride for 5-HT4 receptors in the heart has been implicated in the undesirable cardiac effects of cisapride itself.[medical citation needed]
The conclusion of this study revealed that itopride is devoid of any abnormal effect onQT interval. Therefore, it may be possible that itopride could be considered as a better and certainly safer prokinetic agent than eithercisapride ormosapride, and itopride should also be considered a welcome treatment addition for symptomatic nonulcer dyspepsia and other gastric motility disorders.[12]
Itopride acts as a selective dualD2 receptorantagonist andacetylcholinesterase inhibitor.[5][6]
There is evidence that itopride may have prokinetic effects throughout the gastrointestinal tract from the stomach to the end of the colon.[13] The pharmacokinetics of itopride appear to differ between Asian and Caucasian populations, with Caucasians having 30-50 percent lower blood levels of itopride after oral administration.[14] Itopride poorly penetrates across the blood brain barrier because of its high polarity and thus itopride does not tend to cause anycentral nervous system adverse effects.[7] Itopride has no effect onpotassium channels.[15]
Similarly to other D2 receptor antagonists, itopride has been found to dose-dependently increaseprolactin levels.[6]
After oral administration itopride undergoes rapid and extensive absorption with levels of itopride peaking in the blood plasma after only 35 minutes. Itopride is primarily eliminated via the kidneys having anelimination half-life of approximately 6 hours.[16]
Itopride increasesacetylcholine concentrations by inhibitingdopamine D2 receptors andacetylcholinesterase. Higher acetylcholine increases GIperistalsis, increases the lower esophageal sphincter pressure, stimulates gastric motility, accelerates gastric emptying, and improves gastro-duodenal coordination.[7]
Itopride given as a single dose study found that it also raises levels ofmotilin,somatostatin and lowers levels ofcholecystokinin, as well asadrenocorticotropic hormone. These effects may also contribute to itopride's pharmacology.[17]
Itopride is available under various brand names including Ganaton (Japan, Czech Republic, Russian Federation), Itoprid PMCS (Czech Republic, Slovakia), Itomed (Kyrgyzstan, Kazakhstan, Moldova, Russia, Ukraine, Uzbekistan), Prokit (Poland), and Itogard (Nepal). In Mexico, itopride is sold by Takeda Laboratories under the brand name Dagla. In Bulgaria and other countries of East Europe itopride is sold by Zentiva under the brand name Zirid[18]
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