Cisapride

Cisapride

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Systematic (IUPAC) name
(±)-cis-4-amino-5-chloro-N-(1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-yl)-2-methoxybenzamide
Clinical data
Trade names	Prepulsid, Propulsid
AHFS/Drugs.com	FDA Professional Drug Information
MedlinePlus	a694006
Pregnancy category	AU: B1
Legal status	AU: S4 (Prescription only) UK: POM (Prescription only) US: Withdrawn
Routes of administration	oral (tablets), suspension
Pharmacokinetic data
Bioavailability	30-40%
Protein binding	97.5%
Metabolism	hepatic CYP3A4, intestinal
Biological half-life	10 hours
Excretion	renal, biliary
Identifiers
CAS Number	81098-60-4 Y
ATC code	A03FA02 (WHO)
PubChem	CID: 2769
IUPHAR/BPS	240
DrugBank	DB00604 Y
ChemSpider	2667 Y
UNII	UVL329170W Y
KEGG	D00274 Y
ChEMBL	CHEMBL1729 N
Chemical data
Formula	C23H29ClFN3O4
Molecular mass	465.945 g/mol
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 Pharmaceutica in 1980. In many countries, it has been either withdrawn from the market or had its indications limited because of side-effects.

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In many countries, it has been either withdrawn or had its indications limited because of reports of the side-effect long QT syndrome, which may cause arrhythmias.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-HT 4 receptor subtype. Cisapride also relieves constipation-like symptoms by indirectly stimulating the release of acetylcholine in the muscarinic receptors.

See also

• Serotonin agonist Laxatives
• Benzamide
• Domperidone
• Drug of last resort
• Itopride
• Metoclopramide
• Mosapride

Sources

• Brenner, G. M. (2000). Pharmacology. Philadelphia, PA: W.B. Saunders Company. ISBN 0-7216-7757-6
• Canadian Pharmacists Association (2000). Compendium of Pharmaceuticals and Specialties (25th ed.). Toronto, ON: Webcom. ISBN 0-919115-76-4
• Medline Plus

External links

• Archived Drug Label