Itopride Introduction:

Itopride (INN) (brand name Ganaton) is a prokinetic benzamide derivative unlike domperidone. These
drugs inhibit dopamine and acetylcholine esterase enzyme and have a gastrokinetic effect. Itopride is
indicated for the treatment of functional dyspepsia and other gastrointestinal conditions. It is a
combined D2 receptor antagonist and acetylcholinesterase inhibitor.

Pharmacology
Itopride acts as a selective dual D2 receptor antagonist and acetylcholinesterase inhibitor. There is
evidence that itopride may have prokinetic effects throughout the gastrointestinal tract from the
stomach to the end of the colon. 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. Itopride poorly penetrates across the blood brain barrier because of its high polarity and
thus itopride does not tend to cause any central nervous system adverse effects. Itopride has no effect
on potassium channels. Similarly to other receptor antagonists, itopride has been found to dose-
dependently increase prolactin levels.

Pharmacokinetics
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
an elimination half-life of approximately 6 hours.

Mechanism of action
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.

Itopride given as a single dose study found that it also raises levels of motilin, somatostatin and lowers
levels of cholecystokinin, as well as adrenocorticotropic hormone. These effects may also contribute to
itopride's pharmacology.

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

dyspepsia of a non-ulcer/dysmotility type (gastric "fullness", discomfort, and possible pain)

gastroparesis (delayed gastric emptying), 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.
Adverse drug reactions
The most common side-effects of itopride include mild to moderate abdominal pain and diarrhoea.
Some other side effects that may occur include: rash, giddiness, exhaustion, back or chest pain,
increased salivation, constipation, 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.

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. Raising of prolactin levels is more
common with high dose regimes of itopride.

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, rendering
contraindications or side effects that are not currently known.

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.