Chemistry:Cisapride

Short description: Chemical compound

Cisapride

Clinical data
Trade names	Prepulsid, Propulsid
AHFS/Drugs.com	FDA Professional Drug Information
MedlinePlus	a694006
Pregnancy category	AU: B1
Routes of administration	By mouth (tablets), suspension
ATC code	A03FA02 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) BR: Class C1 (Other controlled substances) UK: POM (Prescription only) US: Withdrawn
Pharmacokinetic data
Bioavailability	30-40%
Protein binding	97.5%
Metabolism	liver CYP3A4, intestinal
Elimination half-life	10 hours
Excretion	kidney, bile duct
Identifiers
IUPAC name (±)-cis-4-amino-5-chloro-N-(1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-yl)-2-methoxybenzamide
CAS Number	81098-60-4 Y
PubChem CID	2769
IUPHAR/BPS	240
DrugBank	DB00604 Y
ChemSpider	2667 Y
UNII	UVL329170W
KEGG	D00274 Y
ChEMBL	ChEMBL1729 N
Chemical and physical data
Formula	C23H29ClFN3O4
Molar mass	465.95 g·mol−1
3D model (JSmol)	Interactive image
SMILES Clc1cc(c(OC)cc1N)C(=O)NC3CCN(CCCOc2ccc(F)cc2)CC3OC
InChI InChI=1S/C23H29ClFN3O4/c1-30-21-13-19(26)18(24)12-17(21)23(29)27-20-8-10-28(14-22(20)31-2)9-3-11-32-16-6-4-15(25)5-7-16/h4-7,12-13,20,22H,3,8-11,14,26H2,1-2H3,(H,27,29) Y Key:DCSUBABJRXZOMT-UHFFFAOYSA-N Y
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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 increases acetylcholine release in the enteric nervous system. It has been sold under the trade names Prepulsid (Janssen-Ortho) and Propulsid (in the United States). It was discovered by Janssen Pharmaceuticals in 1980. In many countries, it has been either withdrawn from the market or had its indications limited due to incidence of serious cardiac side-effects. Propulsid was linked to children's deaths.

The commercial preparations of this drug are the racemic mixture of both enantiomers of the compound. The (+) enantiomer itself has the major pharmacologic effects and does not induce many of the detrimental side-effects of the mixture.

Medical uses

Cisapride has been used for the treatment of gastroesophageal reflux disease (GERD). There is no evidence it is effective for this use in children. It also increases gastric emptying in people with diabetic gastroparesis. Evidence for its use in constipation is not clear.

In many countries, it has been either withdrawn or had its indications limited because of reports of the side-effect long QT syndrome, which may cause arrhythmias. The U.S. Food and Drug Administration (FDA) issued a warning letter to doctors, and cisapride was voluntarily removed from the U.S. market on July 14, 2000. Its use in Europe has also been limited. It was banned in India and in the Philippines in 2011.

Veterinary uses

Cisapride is still available in the United States and Canada for use in animals, and is commonly prescribed by veterinarians to treat megacolon in cats.

Cisapride is also commonly used to treat GI stasis in rabbits, sometimes in conjunction with metoclopramide (Reglan).

Kinetics

Oral bioavailability of cisapride is approximately 33%. It is inactivated primarily by hepatic metabolism by CYP3A4 with a half-life of 10 hours. The dose of the drug should be reduced in case of liver diseases.

Pharmacology and mechanism of action

As a prokinetic agent that increases gastrointestinal motility, cisapride acts as a selective serotonin agonist in the 5-HT₄ receptor subtype. Cisapride also relieves constipation-like symptoms by indirectly stimulating the release of acetylcholine, which acts on muscarinic receptors.

See also

• Domperidone
• Drug of last resort
• Serotonin-agonising laxatives
• Benzamide
• Itopride
• Metoclopramide
• Mosapride

Further reading

• Pharmacology. Philadelphia, PA: W.B. Saunders Company. 2000. ISBN 0-7216-7757-6. 
• Canadian Pharmacists Association (2000). Compendium of Pharmaceuticals and Specialties (25th ed.). Toronto, ON: Webcom. ISBN 0-919115-76-4. 
• "Cisapride". Medline Plus. U.S. National Library of Medicine. https://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a694006.html. 

External links

• Archived Drug Label