Itopride (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...

; brand name Ganaton) is a

prokinetic A prokinetic agent (also gastroprokinetic agent, gastrokinetic agent or propulsive) is a type of drug which enhances gastrointestinal motility by increasing the frequency or strength of contractions, but without disrupting their rhythm. They are us ...

benzamide Benzamide is a organic compound with the chemical formula of C6H5C(O)NH2. It is the simplest amide derivative of benzoic acid Benzoic acid is a white (or colorless) solid organic compound with the formula , whose structure consists of a benz ...

derivative. These drugs inhibit

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

and acetylcholine esterase enzyme and have a

gastrokinetic A prokinetic agent (also gastroprokinetic agent, gastrokinetic agent or propulsive) is a type of drug which enhances gastrointestinal motility by increasing the frequency or strength of contractions, but without disrupting their rhythm. They are u ...

effect. Itopride is indicated for the treatment of functional

dyspepsia Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier t ...

and other gastrointestinal conditions. It is a combined D₂ receptor

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

and

acetylcholinesterase inhibitor Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level and ...

Medical uses

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

of a non-ulcer/dysmotility type (gastric "fullness", discomfort, and possible pain) * gastroparesis (delayed gastric emptying) *

anorexia Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gre ...

heartburn Heartburn, also known as pyrosis, cardialgia or acid indigestion, is a burning sensation in the central chest or upper central abdomen. Heartburn is usually due to regurgitation of gastric acid (gastric reflux) into the esophagus. It is the ma ...

*regurgitation *bloating *nausea and vomiting *other possible gastric, prolactin, or dopamine related conditions 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 Benzamide is a organic compound with the chemical formula of C6H5C(O)NH2. It is the simplest amide derivative of benzoic acid Benzoic acid is a white (or colorless) solid organic compound with the formula , whose structure consists of a benze ...

;

lactation Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process naturally occurs with all sexually mature female mammals, although it may predate mammals. The proces ...

, GI

hemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...

, obstruction or perforation. Itopride may not be indicated for those suffering from

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

or other conditions involving

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

The most common side-effects of itopride include mild to moderate abdominal pain and diarrhoea. Some other side effects that may occur include:

rash A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cr ...

, giddiness, exhaustion, back or chest pain, increased salivation,

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

, sleeping disorders, dizziness,

galactorrhea Galactorrhea ( also spelled galactorrhoea) ( galacto- + -rrhea) or lactorrhea ( lacto- + -rrhea) is the spontaneous flow of milk from the breast, unassociated with childbirth or nursing. Galactorrhea is reported to occur in 5–32% of women. M ...

, and

gynecomastia Gynecomastia (also spelled gynaecomastia) is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse (1 ...

Leukopenia Leukopenia () is a decrease in the number of leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of inf ...

, 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.

Cardiac studies

Itopride belongs to the same

group as

cisapride Cisapride is a gastroprokinetic agent, a drug that increases motility in the upper gastrointestinal tract. It acts directly as a serotonin 5-HT4 receptor agonist and indirectly as a parasympathomimetic. Stimulation of the serotonin receptors incr ...

, a drug found to affect

QT interval The QT interval is a measurement made on an electrocardiogram used to assess some of the electrical properties of the heart. It is calculated as the time from the start of the Q wave to the end of the T wave, and approximates to the time taken ...

and possibly predispose those using it to cardiac

arrhythmias Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...

. However, itopride does not have any adverse effect on the QT interval. 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 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...

enzyme pathway, unlike

and

mosapride Mosapride is a gastroprokinetic agent that acts as a selective 5HT4 agonist. The major active metabolite of mosapride, known as M1, additionally acts as a 5HT3 antagonist, which accelerates gastric emptying throughout the whole of the gastroin ...

, as it is metabolized by a different enzyme set. New molecular studies on guinea pig ventricular

myocytes A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a muscl ...

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

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

. Therefore, it may be possible that itopride could be considered as a better and certainly safer prokinetic agent than either

, and itopride should also be considered a welcome treatment addition for symptomatic nonulcer dyspepsia and other gastric motility disorders.

Pharmacology

Itopride acts as a selective dual D₂ receptor

and

. 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 The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

adverse effects. Itopride has no effect on

potassium channels Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cel ...

. Similarly to other D₂ receptor antagonists, itopride has been found to dose-dependently increase

prolactin Prolactin (PRL), also known as lactotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secreted from the pit ...

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 Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

of approximately 6 hours.

Mechanism of action

Itopride increases

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...

concentrations by inhibiting dopamine D2 receptors and

acetylcholinesterase Acetylcholinesterase (HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme Enzymes () are proteins that a ...

. Higher acetylcholine increases GI

peristalsis Peristalsis ( , ) is a radially symmetrical contraction and relaxation of muscles that propagate in a wave down a tube, in an anterograde direction. Peristalsis is progression of coordinated contraction of involuntary circular muscles, which ...

, 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 Motilin is a 22-amino acid polypeptide hormone in the motilin family that, in humans, is encoded by the ''MLN'' gene. Motilin is secreted by endocrine Mo cells (also referred to as M cells, which are not the same as the M cells, or microfold ce ...

somatostatin Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-couple ...

and lowers levels of

cholecystokinin Cholecystokinin (CCK or CCK-PZ; from Greek ''chole'', "bile"; ''cysto'', "sac"; ''kinin'', "move"; hence, ''move the bile-sac (gallbladder)'') is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and ...

, as well as

adrenocorticotropic hormone Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important c ...

. These effects may also contribute to itopride's pharmacology.

Interactions

Anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous system ...

agents reduce the action of itopride.

Society and culture

Names

Itopride is available under the brand names Ganaton ( JP, CZ, RU),

Abbott Laboratories Abbott Laboratories is an American multinational medical devices and health care company with headquarters in Abbott Park, Illinois, United States. The company was founded by Chicago physician Wallace Calvin Abbott in 1888 to formulate known dr ...

), Itoprid PMCS ( CZ, SK), Itomed ( KG, KZ, MD, RU, UA, UZ) and Prokit ( PL), PRO.MED.CS Praha a.s.), Itogard (Apex Pharmaceuticals, Nepal) and others. In Mexico, itopride (50 mg) is sold by Takeda Laboratories under the brand name Dagla. In Bulgaria and other countries of East Europe itopride (50 mg) is sold by Zentiva under the brand name Zirid

References

External links

*
Abbott Labs "Ganaton"
* {{Portal bar , Medicine Acetylcholinesterase inhibitors Benzamides D2 antagonists AbbVie brands Takeda Pharmaceutical Company brands Motility stimulants Catechol ethers Peripherally selective drugs de:Prokinetikum es:Procinético ja:イトプリド塩酸塩 pl:Leki prokinetyczne