Cisapride

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Cisapride
Cisapride.svg
Cisapride 3D.png
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 cat.
Legal status
Routes oral (tablets), suspension
Pharmacokinetic data
Bioavailability 30-40%
Protein binding 97.5%
Metabolism hepatic CYP3A4, intestinal
Half-life 10 hours
Excretion renal, biliary
Identifiers
CAS number 81098-60-4 YesY
ATC code A03FA02
PubChem CID 2769
IUPHAR ligand 240
DrugBank DB00604
ChemSpider 2667 YesY
UNII UVL329170W YesY
KEGG D00274 YesY
ChEMBL CHEMBL1729 N
Chemical data
Formula C23H29ClFN3O4 
Mol. mass 465.945 g/mol
 N (what is this?)  (verify)

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 U.S.). 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 In many countries, it has been either withdrawn from the market or had its indications limited because of side-effects.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.[1]

Medical uses[edit]

Cisapride has been used for the treatment of gastroesophageal reflux disease (GERD). There is no evidence it is effective for this use in children.[2] It also increases gastric emptying in people with diabetic gastroparesis. Evidence for its use in constipation is not clear.[3]

In many countries, it has been either withdrawn or had its indications limited because of reports of the side-effect long QT syndrome, which may cause arrhythmias.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,[4] and cisapride was voluntarily removed from the U.S. market on July 14, 2000. Its use in Europe has also been limited.[2] It was banned in India and in the Philippines on 2011.[5]

Veterinary uses[edit]

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[edit]

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.[6]

Pharmacology and mechanism of action[edit]

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[edit]

References[edit]

  1. ^ US patent 5955478, Nancy M. Gray, N. M.; Young, J. W, "Methods for treating gastrointestinal motility dysfunction using optically pre (+) cisapride", issued 1999-Sep-21 
  2. ^ a b Maclennan, S; Augood, C; Cash-Gibson, L; Logan, S; Gilbert, RE (Apr 14, 2010). "Cisapride treatment for gastro-oesophageal reflux in children.". The Cochrane database of systematic reviews (4): CD002300. doi:10.1002/14651858.CD002300.pub2. PMID 20393933. 
  3. ^ Aboumarzouk, OM; Agarwal, T; Antakia, R; Shariff, U; Nelson, RL (Jan 19, 2011). "Cisapride for intestinal constipation.". The Cochrane database of systematic reviews (1): CD007780. doi:10.1002/14651858.CD007780.pub2. PMID 21249695. 
  4. ^ "Propulsid (cisapride) Safety Information". Retrieved 2011-07-14. 
  5. ^ "Drugs banned in India". Central Drugs Standard Control Organization, Dte.GHS, Ministry of Health and Family Welfare, Government of India. Retrieved 2013-09-17. 
  6. ^ "Comparative bioavailability of a cisapride suppository and tablet formulation in healthy volunteers" European Journal of Clinical Pharmacology T Hedner et al. Volume 38, Number 6, 629-631, doi:10.1007/BF00278595

Sources[edit]

  • 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[edit]