{{Short description|Chemical compound}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Drugbox | Verifiedfields = changed | verifiedrevid = 460039920 | IUPAC_name = (±)-''cis''-4-amino-5-chloro-''N''-(1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-yl)-2-methoxybenzamide | image = Cisapride enantiomers labelled.svg | image_class = skin-invert-image | width = 350px | image2 = Cisapride enantiomers ball-and-stick models from xtal 1997.png | image_class2 = bg-transparent | width2 = 350px <!--Clinical data--> | tradename = Prepulsid, Propulsid | Drugs.com = {{drugs.com|pro|propulsid}} | MedlinePlus = a694006 | pregnancy_AU = B1 | pregnancy_category = | legal_AU = S4 | legal_BR = C1 | legal_BR_comment = <ref>{{cite web | author = Anvisa | date = 2023-03-31 | title = RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial | language = pt-BR | publisher = Diário Oficial da União | url = https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 | access-date = 2023-08-16 | archive-date = 2023-08-03 | 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 | author-link = Brazilian Health Regulatory Agency | trans-title = Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control | url-status = live | publication-date = 2023-04-04 }}</ref> | legal_UK = POM | legal_US_comment = Withdrawn | legal_status = | routes_of_administration = By mouth (tablets), suspension <!--Pharmacokinetic data--> | bioavailability = 30-40% | protein_bound = 97.5% | metabolism = liver CYP3A4, intestinal | elimination_half-life = 10 hours | excretion = kidney, bile duct <!--Identifiers--> | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 81098-60-4 | ATC_prefix = A03 | ATC_suffix = FA02 | ATC_supplemental = | PubChem = 2769 | IUPHAR_ligand = 240 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00604 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 2667 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = UVL329170W | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00274 | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 1729 <!--Chemical data--> | C=23 | H=29 | Cl=1 | F=1 | N=3 | O=4 | smiles = Clc1cc(c(OC)cc1N)C(=O)NC3CCN(CCCOc2ccc(F)cc2)CC3OC | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 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) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = DCSUBABJRXZOMT-UHFFFAOYSA-N }} '''Cisapride''' is a gastroprokinetic agent, a drug that increases motility in the upper gastrointestinal tract. It acts directly as a serotonin 5-HT<sub>4</sub> 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<ref>{{cite web | title = Propulsid To Go Off Market - Warning | website = MedicineNet | url = https://www.medicinenet.com/propulsid_to_go_off_market_-_warning/views.htm | access-date = 2021-12-25 }}</ref> and its being linked to children's deaths.<ref>{{cite web | date = 2000-12-20 | title = PROPULSID: A Heartburn Drug, Now Linked to Children's Deaths | language = en-US | website = Los Angeles Times | url = https://www.latimes.com/nation/la-122001propulsid-story.html | access-date = 2021-12-25 }}</ref>
The commercial preparations of this drug are the racemic mixture of both enantiomers 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 = Gray NM, Young JW |title= Methods for treating gastrointestinal motility dysfunction using optically pre (+) cisapride }}</ref>
==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.<ref name=GERD2010>{{cite journal | vauthors = Maclennan S, Augood C, Cash-Gibson L, Logan S, Gilbert RE | date = April 2010 | title = Cisapride treatment for gastro-oesophageal reflux in children | journal = The Cochrane Database of Systematic Reviews | volume = 2010 | issue = 4 | article-number = CD002300 | doi = 10.1002/14651858.CD002300.pub2 | pmc = 7138252 | pmid = 20393933 }}</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 | date = January 2011 | title = Cisapride for intestinal constipation | journal = The Cochrane Database of Systematic Reviews | issue = 1 | article-number = CD007780 | doi = 10.1002/14651858.CD007780.pub2 | pmid = 21249695 }}</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 may cause arrhythmias. The U.S. Food and Drug Administration (FDA) issued a warning letter to doctors,<ref>{{cite web | date = January 25, 2000 | title = "Cardiac contraindications included in new FDA warnings about Propulsid" | publisher = medscape.com | url = https://www.medscape.com/viewarticle/783710 | access-date = 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 | title = Drugs banned in India | publisher = Central Drugs Standard Control Organization, Dte.GHS, Ministry of Health and Family Welfare, Government of India | url = http://cdsco.nic.in/html/drugsbanned.html | access-date = 2013-09-17 | archive-date = 2015-02-21 | archive-url = https://web.archive.org/web/20150221053621/http://cdsco.nic.in/html/drugsbanned.html }}</ref>
==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.<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 | date = 1990 | title = Comparative bioavailability of a cisapride suppository and tablet formulation in healthy volunteers | journal = European Journal of Clinical Pharmacology | volume = 38 | issue = 6 | pages = 629–631 | doi = 10.1007/bf00278595 | pmid = 2373139 | 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-HT<sub>4</sub> receptor subtype. Cisapride also relieves constipation-like symptoms by indirectly stimulating the release of acetylcholine, which acts on muscarinic receptors.
It may increase the QT interval, which can cause serious ventricular arrhythmias. This action results from interactions with the hERG channel.<ref name=GoodmanGilman>{{cite book | vauthors = Sharkey KA, MacNaughton WK | date = 2018 | veditors = Brunton LL, Hilal-Dandan R, Knollmann BC | title = Goodman & Gilman's The Pharmacological Basis of Therapeutics | publisher = New York: McGraw-Hill | page = 924 | isbn = 978-1-259-58473-2 }}</ref>
== See also == *Domperidone *Drug of last resort *Serotonin-agonising laxatives *Benzamide *Itopride *Metoclopramide *Mosapride *Prucalopride
== References == {{reflist}}
== Further reading == {{refbegin}} * {{cite book | vauthors = Brenner GM | date = 2000 | title = Pharmacology | publisher = W.B. Saunders Company | isbn = 978-0-7216-7757-6 | location = Philadelphia, PA }} * {{cite book | author = Canadian Pharmacists Association | date = 2000 | title = Compendium of Pharmaceuticals and Specialties | publisher = Webcom | edition = 25th | isbn = 978-0-919115-76-7 | location = Toronto, ON }} * {{cite web | title = Cisapride | work = Medline Plus | publisher = U.S. National Library of Medicine | url = https://www.medlineplus.gov/druginfo/meds/a694006.html }} {{refend}}
== External links == * [https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=13266 Archived Drug Label]
{{Propulsives}} {{Serotonergics}} {{Cholinergics}} {{Ion channel modulators}}
Category:4-Amino-N-(3-(diethylamino)propyl)-2-methoxybenzamides Category:Serotonin receptor agonists Category:HERG blocker Category:CYP2D6 inhibitors Category:Withdrawn drugs Category:Chloroarenes Category:Piperidines Category:4-Fluorophenyl compounds Category:Janssen Pharmaceutica Category:Belgian inventions