Cisapride: Difference between revisions

{{Short description|Chemical compound}}

| verifiedrevid =

| pregnancy_AU = B1

| pregnancy_category =

| legal_AU = S4

| legal_BR = C1

| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>

| legal_UK = POM

| legal_US_comment = Withdrawn

| legal_status =

| routes_of_administration = tablets, suspension

| metabolism = , intestinal

| excretion = ,

| KEGG_Ref = {{keggcite||kegg}}

| ChEMBL = 1729

<!--Chemical data-->

| C=23 | H=29 | Cl=1 | F=1 | N=3 | O=4

'''Cisapride''' is a [[gastroprokinetic agent]], a [[pharmaceutical drug|drug]] increases [[motility]] in the upper [[gastrointestinal tract]]. It acts as a [[serotonin]] [[5-HT4 receptor|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 ). It was discovered by [[Janssen ]] in 1980. In many countries it has been either withdrawn from the market or had its indications limited of effects.

The commercial preparations of this drug are the [[racemic]] mixture of both [[enantiomer]]s of the compound. The (+) enantiomer itself<!-- what is the absolute configuration? --> has the major pharmacologic effects and does not induce many of the detrimental side-effects of the mixture.<ref>{{US patent reference |number = 5955478 |y= 1999 |m= Sep |d= 21 | inventor = , Young |title= Methods for treating gastrointestinal motility dysfunction using optically pre (+) cisapride }}</ref>

== 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.<ref name=GERD2010>{{cite journal | vauthors = Maclennan S, Augood C, Cash-Gibson L, Logan S, Gilbert RE | title = Cisapride treatment for gastro-oesophageal reflux in children | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD002300 | date = April 2010 | volume = 2010 | pmid = 20393933 | doi = 10.1002/14651858.CD002300.pub2 | pmc = 7138252 | url = https://researchonline.lshtm.ac.uk/3792/1/3792.pdf }}</ref> It also increases gastric emptying in people with diabetic [[gastroparesis]]. Evidence for its use in [[constipation]] is not clear.<ref name=Cochrane2011>{{cite journal | vauthors = Aboumarzouk OM, Agarwal T, Antakia R, Shariff U, Nelson RL | title = Cisapride for intestinal constipation | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD007780 | date = January 2011 | pmid = 21249695 | doi = 10.1002/14651858.CD007780.pub2 }}</ref>

In many countries it has been either withdrawn or had its indications limited because of reports of the side-effect [[long QT syndrome]] which [[arrhythmia]]s. The [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] (FDA) issued a warning letter to doctors,<ref>{{cite web

|url = https://www.medscape.com/viewarticle/783710

|title = "Cardiac contraindications included in new FDA warnings about Propulsid"

|author =

|date = January 25, 2000

|publisher = medscape.com

|accessdate = 10 May 2021

}}</ref> and cisapride was voluntarily removed from the U.S. market on July 14, 2000. Its use in Europe has also been limited.<ref name=GERD2010/> It was banned in India and in the Philippines in 2011.<ref name=ban>{{cite web|url=http://cdsco.nic.in/html/drugsbanned.html|title=Drugs banned in India|publisher=Central Drugs Standard Control Organization, Dte.GHS, Ministry of Health and Family Welfare, Government of India|access-date=2013-09-17|url-status=dead|archive-url=https://web.archive.org/web/20150221053621/http://cdsco.nic.in/html/drugsbanned.html|archive-date=2015-02-21}}</ref>

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

Cisapride is also commonly used to treat 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.<ref name="pmid2373139">{{cite journal | vauthors = Hedner T, Hedner J, Gelin-Friberg A, Huang ML, Van de Poel S, Woestenborghs R, Van Peer A, Heykants J | title = Comparative bioavailability of a cisapride suppository and tablet formulation in healthy volunteers | journal = European Journal of Clinical Pharmacology | volume = 38 | issue = 6 | pages = 629–31 | date = 1990 | pmid = 2373139 | doi = 10.1007/bf00278595 | s2cid = 33641651 }}</ref>

==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 receptor]]s.

*[[Drug of last resort]]

*[[Laxative#Serotonin agonist|Serotonin-agonising laxatives]]

*[[Benzamide]]

==References==

== Further reading ==

{{refbegin}}

* Brenner 2000 Pharmacology Philadelphia, PA W.B. Saunders Company 0-7216-7757-6

* Canadian Pharmacists Association 2000 Compendium of Pharmaceuticals and Specialties 25th Toronto, ON Webcom 0-919115-76-4

* ://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a694006.html Medline Plus

{{refend}}

==External ==

{{Cholinergics}}

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