Itopride

Itopride

File:Itopride.png
Systematic (IUPAC) name
N-[[4-(2-Dimethylaminoethoxy)phenyl]methyl]-3,4-dimethoxybenzamide
Clinical data
Routes of administration	Oral
Legal status
Legal status	℞ (Prescription only)
Identifiers
CAS Number	122898-67-3
ATC code	none
PubChem	CID 3792
Chemical data
Formula	C20H26N2O4
Molar mass	358.43 g/mol[[]]

Itopride (INN) is a prokinetic benzamide derivative unlike metoclopramide or domperidone. These drugs inhibit dopamine and have a gastrokinetic effect. Itopride is indicated for the treatment of functional dyspepsia and other gastrointestinal conditions.

It has the tradename Ganaton and is marketed by Abbott Laboratories.

Itopride is not currently approved by the U.S. Food and Drug Administration (FDA) for use in the United States, nor is it yet approved in the United Kingdom. This may explain the apparent lack of patient information available in English compared to other similar classes of medication.

Clinical use

File:Ganaton2a.jpg

A blister package of Ganaton (Itopride) 50 mg tablets intended for distribution in the Slovak Republic.

Typically, itopride is indicated in the treatment of GI symptoms caused by reduced GI motility:

• dyspepsia of a non-ulcer type (gastric "fullness", discomfort, and possible pain)
• anorexia
• heartburn
• regurgitation
• bloating
• nausea and vomiting
• other possible gastric, prolactin, or dopamine related conditions

Itopride is typically taken three times a day. The dose is usually taken on an empty stomach about an hour before meals. However, the dosage and details of administration may vary depending on the patient’s age, symptoms, and other factors.

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 of functional 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.

Contraindications and precautions

Itopride is a relatively new drug and it is not currently approved for normal prescribed use nor OTC use in either the US nor the UK. However, this does not necessarily indicate that itopride is not effective or safe.

Patients taking itopride should report any side-effects to their treating physician.

Itopride is contraindicated in hypersensitivity to itopride or benzamides; lactation, GI hemorrhage, obstruction or perforation. Itopride may not be indicated for those suffering from Parkinson's disease or other conditions involving dopamine regulation issues. Itopride should be used with special caution in the young and the elderly. Little information is available at this time regarding the safe use of itopride during pregnancy.

Adverse drug reactions

Some common side-effects of itopride may include: rash, diarrhea, giddiness, exhaustion, back or chest pain, increased salivation, constipation, abdominal pain, headache, sleeping disorders, dizziness, galactorrhea, and gynecomastia.

Other side effects may also be present.

Leukopenia, a reduction in the normal level of white blood cells, can be a potentially life-threatening reaction to itopride.

Cardiac studies

Itopride belongs to the same benzamide group as cisapride, a drug which was found to effect QT interval and possibly predispose those using it to cardiac arrhythmias. This resulted in cisapride being voluntarily removed from the U.S. market on July 14, 2000 after a warning letter was issued by the FDA which mentioned these effects. An obvious concern due to similarities between cisapride and itopride led to several preclinical studies being undertaken to evaluate the cardiac safety profile of itopride to see if it had a similar effect on QT interval in animals. These studies indicated that unlike cisapride, itopride was devoid of the potential to cause prolongation of the QT interval and posed no known risk of cardiac arrhythmias.

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 the cytochrome P450 enzyme pathway unlike cisapride and mosapride as it is metabolized by a different enzyme set. New molecular studies on guinea-pig ventricular myocytes 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 the 5-HT₄ receptors unlike other benzamides 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.

The conclusion of this study revealed that itopride is devoid of any abnormal effect on QT interval. Therefore it may be possible that itopride could be considered as a better and certainly safer prokinetic agent than either cisapride or mosapride and itopride should also be considered a welcome treatment addition for symptomatic nonulcer dyspepsia and other gastric motility disorders.

Mechanism of action

File:Ganaton1.jpg

Ganaton (Itopride) 50 mg tablets. Engraving says "HC 803"

Itopride increases acetylcholine concentrations by inhibiting dopamine D2 receptors and acetylcholinesterase. Higher acetylcholine increases GI peristalsis, increases the lower esophageal sphincter pressure, stimulates gastric motility, accelerates gastric emptying, and improves gastro-duodenal coordination.

Interactions

Anticholinergic agents reduce the action of itopride. It is worth noting that itopride is a relatively new drug and that it is therefore possible that other drugs may interact with itopride which are not currently known.

See also

• Benzamides

External links

• Itopride on www.cimsasia.com
• Abbott Labs "Ganaton"
• "Itopride in Functional Dyspepsia:a Dose Finding Study" at Clinicaltrials.gov

de:Prokinetikum ja:イトプリド塩酸塩