Domperidone

Domperidone

Systematic (IUPAC) name
5-chloro-1-(1-[3-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl]piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one
Identifiers
CAS number	57808-66-9
ATC code	A03FA03
PubChem	3151
DrugBank	APRD00418
ChemSpider	3039
Chemical data
Formula	C22H24ClN5O2
Mol. mass	425.911 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	High
Protein binding	91–93%
Metabolism	Hepatic and intestinal (first-pass)
Half life	7 hours
Excretion	Breast milk, renal
Therapeutic considerations
Pregnancy cat.	Not classified (US)
Legal status	Not approved for use or sale: US; prescription medicine: India, Australia, Canada, Israel; Over the Counter (OTC): UK, Belgium, Egypt, Ireland, Italy, Japan, Netherlands, South Africa, Switzerland, China, Russia, Slovakia, Malta, South Korea, and Romania[1]
Routes	Oral, intravenous, rectal
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Domperidone (trade names Motilium, Motillium, Motinorm and Costi) is an antidopaminergic drug, developed by Janssen Pharmaceutica, and used orally, rectally or intravenously, generally to suppress nausea and vomiting. It has also been used to stimulate lactation.

Uses

Gastrointestinal problems

There is some evidence that domperidone has antiemetic activity.^[2] Domperidone is used, together with metoclopramide, cyclizine, and 5HT₃ receptor antagonists (such as granisetron) in the treatment of nausea and vomiting.

Domperidone is a first choice antiemetic in most countries.^{[citation needed]} However, it is not approved for prescription in the US. Although it has never been officially approved for use in the United States, domperidone is sometimes purchased from pharmacies in other countries for this purpose.

It can be used in patients with Parkinson's disease^[3] because, unlike metoclopramide^[4], domperidone does not cross the blood-brain barrier.

Domperidone has also been found effective in the treatment of gastroparesis,^[5] a stomach motility condition, and for paediatric gastroesophageal reflux (infant vomiting).

Lactation

The hormone prolactin stimulates lactation in humans, and its release is inhibited by the dopamine secreted by the hypothalamus. Domperidone, by acting as an anti-dopaminergic, results in increased prolactin secretion, and thus promotes lactation.

Since, according to the U.S. Food and Drug Administration (FDA), domperidone is not approved for enhanced lactation in any country,^[6] it is sometimes self-prescribed from original research or prescribed "off-label" for this use in countries around the world.^[7]

Controversy

Janssen Pharmaceutical has brought domperidone before the FDA several times in the last two decades, with the most recent effort in the 1990s. Numerous U.S. clinical drug trials have demonstrated its safety and efficacy in dealing with gastroparesis symptoms, but the FDA turned down Janssen's application for domperidone, even though the FDA's division of gastrointestinal drugs had approved domperidone.^[8]

In June 2004, the United States' main regulation agency, the FDA, issued a letter warning women not to take domperidone, citing unknown risks to parents and infants, and warned pharmacies that domestic sale was illegal, and that import shipments from other countries would be searched and seized. Domperidone is excreted in breast milk, and no studies on its effects on breastfeeding infants have been reported in the literature. Individual incidents of problems with the drug include cardiac arrest and arrhythmia, complications with other medications, as well as complications with improper intravenous use^[7]. A recent paper suggests there may be increased risk of seizures to neonates of mothers taking oral domperidone^[9].

Some doctors and pharmacists do not fully accept the FDA's reasoning and still favor domperidone's use in increasing milk supply. Such doctors and pharmacists claim the drug is safe in the doses given for this purpose but have no evidential data or studies to base their claim.^[10] The American Academy of Pediatrics considers domperidone "usually compatible with breastfeeding".^[11]

There is a new controversy in Britain regarding lethal levels of sodium found in children who are administered this drug. It is now subject to a medical review following a number of criminal trials where parents were charged with child abuse by salt poisoning based on hypernatremia in the affected children.^[12] Recent studies also cite increased QT intervals in neonates taking Domperidone. ^[13].

Pharmacology

Domperidone blocks the action of dopamine. It has strong affinities for the D₂ and D₃ dopamine receptors ^[14], which are found in the chemoreceptor trigger zone, located just outside the blood brain barrier, which - among others - regulates nausea and vomiting (area postrema on the floor of the fourth ventricle and rhomboid fossa).

See also

• itopride
• metoclopramide
• benzamide
• cisapride

Brand

Many brand names and combinations of the drug exist. The combination of domperidone and pantoprazole is marketed as Dompan by Medley Pharmaceuticals. Domperidone is sold as Motinorm by GlaxoSmithKline, and as Motis by Saba in Turkey. In India for Paediatric purpose Domperidone is available as Domperi Suspension(Domperidone 1 mg/ml, 30 ml Suspension;Ipca Laboratories Ltd, Mumbai)[1]and Domstal(Torrent Pharmaceuticals Ltd.)[2]

References

External links

• GPDA letter to the FDA about domperidone for gastroparesis