Editing Domperidone (section)

{{Short description|Peripheral D2 receptor antagonist}}
{{Distinguish|Droperidol}}
{{Use dmy dates|date=June 2024}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Watchedfields = changed
| verifiedrevid = 458442916
| image = Domperidone 2D structure.svg
| image_class = skin-invert-image
| width = 250
| alt = 
| image2 = Domperidone-from-xtal-3D-bs-17.png
| image_class2 = bg-transparent
| width2 = 250
| alt2 =

<!-- Clinical data -->
| pronounce = 
| tradename = Motilium, others
| Drugs.com = {{drugs.com|CONS|domperidone}}
| MedlinePlus = 
| DailyMedID = <!-- DailyMed may use generic or brand name (generic name preferred) -->
| pregnancy_AU = B2
| pregnancy_AU_comment = <ref>{{cite web | title=Motilium Product Information | website=[[Therapeutic Goods Administration]] (TGA) | date=10 June 2024 | url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2023-PI-02610-1 | access-date=10 June 2024}}</ref>
| pregnancy_category = 
| routes_of_administration = [[Oral administration|By mouth]], [[rectal administration|rectal]]<ref name="mechanismforantiemetic"/>
| class = [[Dopamine antagonist|D<sub>2</sub> receptor antagonist]]; [[Prolactin releaser]]
| ATC_prefix = A03
| ATC_suffix = FA03
| ATC_supplemental = {{ATCvet|P51|DX06}}

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment = 
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment = 
| legal_CA = Rx-only
| legal_CA_comment = <ref>{{cite web | title=Motilium product information | website=[[Health Canada]] | date=7 January 2002 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=10691 | access-date=10 June 2024}}</ref>
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment = 
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment = 
| legal_UK = POM
| legal_UK_comment = <ref>{{cite web | title=Motilium Summary of Product Characteristics (SmPC) | website=(emc) | date=11 March 2024 | url=https://www.medicines.org.uk/emc/product/4177/smpc | access-date=10 June 2024}}</ref>
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_US_comment = 
| legal_EU = Rx-only
| legal_EU_comment = <ref>{{cite web | title=Motilium referral | website=[[European Medicines Agency]] (EMA) | date=31 October 2000 | url=https://www.ema.europa.eu/en/medicines/human/referrals/motilium | access-date=10 June 2024}}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment = 
| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->
| bioavailability = Oral: 13–17%<ref name="mechanismforantiemetic"/><ref name="Rose2004">{{cite book|vauthors=Rose S|title=Gastrointestinal and Hepatobiliary Pathophysiology|url=https://books.google.com/books?id=1W0JYuzTZsAC&pg=PA523|date=October 2004|publisher=Hayes Barton Press|isbn=978-1-59377-181-2|pages=523–}}{{Dead link|date=August 2023 |bot=InternetArchiveBot |fix-attempted=yes }}</ref><br />Intramuscular: 90%<ref name="mechanismforantiemetic"/>
| protein_bound = ~92%<ref name="mechanismforantiemetic"/>
| metabolism = [[Liver|Hepatic]] ([[CYP3A4]]/[[CYP3A5|5]]) and [[intestine|intestinal]] ([[first pass effect|first-pass]])<ref name="mechanismforantiemetic"/><ref name="SimardMichaud2008">{{cite journal | vauthors = Simard C, Michaud V, Gibbs B, Massé R, Lessard E, Turgeon J | title = Identification of the cytochrome P450 enzymes involved in the metabolism of domperidone | journal = Xenobiotica; the Fate of Foreign Compounds in Biological Systems | volume = 34 | issue = 11–12 | pages = 1013–1023 | year = 2008 | pmid = 15801545 | doi = 10.1080/00498250400015301 | s2cid = 27426219 }}</ref>
| metabolites = All inactive<ref name="mechanismforantiemetic"/><ref name="SimardMichaud2008" />
| onset = 30–60 minutes<ref name="NHS-Domperidone">{{Cite web|url=https://www.nhs.uk/medicines/domperidone/|title = Domperidone: Anti-sickness medicine used to treat nausea and vomiting|date = 7 January 2020}}</ref>
| elimination_half-life = 7–9 hours<ref name="EMC-Domperidone" /><ref name="mechanismforantiemetic"/><ref name="Rose2004" />
| duration_of_action = 
| excretion = [[Feces]]: 66%<ref name="mechanismforantiemetic"/><br />[[Urine]]: 32%<ref name="mechanismforantiemetic"/><br />[[Breast milk]]: small quantities<ref name="mechanismforantiemetic"/>

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 57808-66-9
| CAS_supplemental = 
| PubChem = 3151
| IUPHAR_ligand = 965
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01184
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 3039
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 5587267Z69
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D01745
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 31515
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 219916
| NIAID_ChemDB = 
| PDB_ligand = 
| synonyms = R-33812; R33812; KW-5338; KW5338; NSC-299589; NSC299589

<!-- Chemical and physical data -->
| IUPAC_name = 5-Chloro-1-(1-[3-(2-oxo-2,3-dihydro-1''H''-benzo[''d'']imidazol-1-yl)propyl]piperidin-4-yl)-1''H''-benzo[''d'']imidazol-2(3''H'')-one
| C=22 | H=24 | Cl=1 | N=5 | O=2
| SMILES = Clc1cc2c(cc1)N(C(=O)N2)C5CCN(CCCN4c3ccccc3NC4=O)CC5
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C22H24ClN5O2/c23-15-6-7-20-18(14-15)25-22(30)28(20)16-8-12-26(13-9-16)10-3-11-27-19-5-2-1-4-17(19)24-21(27)29/h1-2,4-7,14,16H,3,8-13H2,(H,24,29)(H,25,30)
| StdInChI_comment = 
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = FGXWKSZFVQUSTL-UHFFFAOYSA-N
| density = 
| density_notes = 
| melting_point = 242.5
| melting_high = 
| melting_notes = 
| boiling_point = 
| boiling_notes = 
| solubility = 
| sol_units = 
| specific_rotation = 
}}

<!-- Definition and medical uses -->
'''Domperidone''', sold under the brand name '''Motilium''' among others, is a [[dopamine antagonist]] [[medication]] which is used to treat [[nausea]] and [[vomiting]] and certain [[gastrointestinal symptom|gastrointestinal problem]]s like [[gastroparesis]] (delayed [[gastric emptying]]). It raises the level of [[prolactin]] in the human body and is used [[off label]] to induce and promote [[lactation|breast milk production]].<ref name="mechanismforantiemetic">{{cite journal | vauthors = Reddymasu SC, Soykan I, McCallum RW | title = Domperidone: review of pharmacology and clinical applications in gastroenterology | journal = The American Journal of Gastroenterology | volume = 102 | issue = 9 | pages = 2036–2045 | date = September 2007 | pmid = 17488253 | doi = 10.1111/j.1572-0241.2007.01255.x | s2cid = 22575456 }}</ref><ref name="pmid10332535">{{cite journal | vauthors = Barone JA | title = Domperidone: a peripherally acting dopamine2-receptor antagonist | journal = The Annals of Pharmacotherapy | volume = 33 | issue = 4 | pages = 429–440 | date = April 1999 | pmid = 10332535 | doi = 10.1345/aph.18003 | s2cid = 39279569 }}</ref> It may be taken [[oral administration|by mouth]] or [[rectal]]ly.<ref name="mechanismforantiemetic"/><ref name="ema" /><ref name="mhra">{{Cite web |url=http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con076114.pdf |title=Motilium INSTANTS PL 13249/0028 |date=23 February 2010 |publisher=[[Medicines and Healthcare products Regulatory Agency]] |access-date=31 October 2014 |archive-url=https://web.archive.org/web/20141213170157/http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con076114.pdf |archive-date=13 December 2014 |url-status=dead  }}</ref>

<!-- Side effects and mechanism -->
[[Side effect]]s may include [[headache]], anxiety, [[dry mouth]], [[abdominal cramp]]s, [[diarrhea]], and [[hyperprolactinemia|elevated prolactin level]]s.<ref name=BNF79>{{cite book |title=BNF 79 : March 2020. |date=2020 |publisher=Royal Pharmaceutical Society |location=London |isbn=9780857113658|page=444}}</ref><ref name="mechanismforantiemetic"/><ref name="pmid10332535" /><ref name="Henderson2003">{{cite journal | vauthors = Henderson A | title = Domperidone. Discovering new choices for lactating mothers | journal = AWHONN Lifelines | volume = 7 | issue = 1 | pages = 54–60 | year = 2003 | pmid = 12674062 | doi = 10.1177/1091592303251726 }}</ref> Secondary to increased prolactin levels, [[breast disorder|breast changes]], [[galactorrhea|milk outflow]], [[menstrual disorder|menstrual irregularities]], and [[hypogonadism]] can occur.<ref name="mechanismforantiemetic"/><ref name="pmid10332535" /><ref name="Henderson2003" /> Domperidone may also cause [[QT prolongation]] and has rarely been associated with serious [[cardiac complication]]s such as [[sudden cardiac death]].<ref name="pmid26649742" /><ref name="pmid20394569" /><ref name="pmid24147629" /><ref name="pmid26117678" /> However, the risks are small and occur more with high doses.<ref name="pmid26117678" /><ref name="MarziWeitz2015" /> Domperidone acts as a [[peripherally selective drug|peripherally selective]] [[receptor antagonist|antagonist]] of the [[dopamine]] [[D2 receptor|D<sub>2</sub>]] and [[D3 receptor|D<sub>3</sub> receptor]]s.<ref name="mechanismforantiemetic"/><ref name="pmid10332535" /> Due to its low entry into the [[brain]], the side effects of domperidone are different from those of other dopamine receptor antagonists like [[metoclopramide]] and it produces little in the way of [[central nervous system]] adverse effects.<ref name="mechanismforantiemetic"/><ref name="pmid10332535"/> However, domperidone can nonetheless increase prolactin levels as the [[pituitary gland]] is outside of the [[blood–brain barrier]].<ref name="pmid25475074">{{cite journal | vauthors = Paul C, Zénut M, Dorut A, Coudoré MA, Vein J, Cardot JM, Balayssac D | title = Use of domperidone as a galactagogue drug: a systematic review of the benefit-risk ratio | journal = Journal of Human Lactation | volume = 31 | issue = 1 | pages = 57–63 | date = February 2015 | pmid = 25475074 | doi = 10.1177/0890334414561265 | s2cid = 7978585 }}</ref>

<!-- History, society, and culture -->
Domperidone was discovered in 1974 and was introduced for medical use in 1979.<ref name="pmid18507654" /><ref name="dd" /><ref name="WilliamAndrewPublishing2013" /> It was developed by [[Janssen Pharmaceutica]].<ref name="pmid18507654" /><ref name="dd" /> Domperidone is available [[over-the-counter]] in many countries, for instance in Europe and elsewhere throughout the world.<ref name="FaisVermiglio2015" /><ref name="mechanismforantiemetic"/> It is not approved for use in the United States.<ref name="FDA 20231212" /><ref name="pmid15451832" /><ref name="mechanismforantiemetic"/> However, it is available in the United States for people with severe and treatment-refractory gastrointestinal motility problems under an [[expanded access]] individual-patient [[investigational new drug]] application.<ref name="FDA 20231212">{{cite web | url=https://www.fda.gov/drugs/investigational-new-drug-ind-application/how-request-domperidone-expanded-access-use | archive-url=https://web.archive.org/web/20190518202956/https://www.fda.gov/drugs/investigational-new-drug-ind-application/how-request-domperidone-expanded-access-use | url-status=dead | archive-date=18 May 2019 | title=How to Request Domperidone for Expanded Access Use | website=U.S. [[Food and Drug Administration]] (FDA) | date=12 December 2023 }}</ref> An [[structural analog|analogue]] of domperidone called [[deudomperidone]] is under development for potential use in the United States and other countries.<ref name="AdisInsight-Deudomperidone">{{Cite web|url=https://adisinsight.springer.com/drugs/800050807|title=Deudomperidone - CinRx Pharma - AdisInsight}}</ref><ref name="pmid33471485">{{cite journal | vauthors = Heckroth M, Luckett RT, Moser C, Parajuli D, Abell TL | title = Nausea and Vomiting in 2021: A Comprehensive Update | journal = Journal of Clinical Gastroenterology | volume = 55 | issue = 4 | pages = 279–299 | date = April 2021 | pmid = 33471485 | pmc = 7933092 | doi = 10.1097/MCG.0000000000001485 }}</ref><ref name="WoMcCallumGonzalez2021">{{cite book | editor-first = | title = Gastroparesis | vauthors = Wo JM, McCallum RW, Gonzalez Z | chapter = Antiemetic therapy for gastroparesis | date = 2021 | pages = 341–359 | publisher = Elsevier | doi = 10.1016/B978-0-12-818586-5.00025-9 | isbn = 9780128185865| s2cid = 225132800| url = }}</ref>

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