Ergometrine: Difference between revisions

{{Short description|Lysergamide}}

{{Drugbox

| Watchedfields = changed

| verifiedrevid = 443732517

| IUPAC_name = (6a''R'',9''R'')-''N''-((''S'')-1-Hydroxypropan- 2-yl)-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-''fg'']quinoline-9-carboxamide

| image = Ergonovine-skeletal.svg

| width = 150px

<!--Clinical data-->

| tradename = Ergometrine Maleate, Ergonovine Maleate, Ergotrate, Ergotrate Maleate, Ergostat, Syntometrine, others<ref name="MortonHall1999" /><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA397|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=397–}}</ref>

| Drugs.com = {{drugs.com|monograph|ergonovine-maleate}}

| pregnancy_category = X

| legal_AU =

| legal_BR = D1

| 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=2023-08-15 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>

| legal_CA = Schedule VI

| legal_UK =

| legal_US = Rx only

| legal_status =

| routes_of_administration = [[Oral administration|By mouth]]

<!--Pharmacokinetic data-->

| bioavailability =

| protein_bound =

| elimination_half-life = 2-phase (10 min; 2 hrs)

| metabolism = [[Liver]] (partly [[CYP3A4]])

| excretion = [[Biliary]]

<!--Identifiers-->

| IUPHAR_ligand = 148

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 60-79-7

| ATC_prefix = G02

| ATC_suffix = AB03

| PubChem = 443884

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB01253

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D07905

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 4822

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 119443

| synonyms = ergonovine; ''d''-lysergic acid β-propanolamide; ''d''-lysergic acid α-hydroxymethylethylamide

<!--Chemical data-->

| C=19 | H=23 | N=3 | O=2

| SMILES = [H][C@@]12Cc3c[nH]c4cccc(C1=C[C@@H](C(=O)N[C@@H](C)CO)CN2C)c34

<!-- Definition and medical uses -->

'''Ergometrine''', also known as '''ergonovine''' and sold under the brand names '''Ergotrate''', '''Ergostat''', and '''Syntometrine''' among others, is a medication used to cause contractions of the [[uterus]] to treat [[postpartum hemorrhage|heavy vaginal bleeding after childbirth]].<ref name=AHFS2015>{{cite web|title=Ergonovine Maleate|url=https://www.drugs.com/monograph/ergonovine-maleate.html|publisher=The American Society of Health-System Pharmacists|access-date=1 December 2015|url-status=live|archive-url=https://web.archive.org/web/20151225224708/http://www.drugs.com/monograph/ergonovine-maleate.html|archive-date=2015-12-25}}</ref><ref name="MortonHall1999">{{cite book| vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=mqaOMOtk61IC&pg=PA113|date=31 October 1999|publisher=Springer Science & Business Media|isbn=978-0-7514-0499-9|pages=113–}}</ref> It can be used either by mouth, by [[intramuscular|injection into a muscle]], or [[intravenous|injection into a vein]].<ref name=AHFS2015/> It begins working within 15 minutes when taken by mouth and is faster in onset when used by injection.<ref name=AHFS2015/> Effects last between 45 and 180 minutes.<ref name=AHFS2015/>

<!-- Side effects and mechanism -->

Common side effect include [[hypertension|high blood pressure]], vomiting, [[seizure]]s, headache, and [[hypotension|low blood pressure]].<ref name=AHFS2015/> Other serious side effects include [[ergotism]].<ref name=AHFS2015/> It was originally made from the [[rye ergot fungus]] but can also be made from [[lysergic acid]].<ref name=Rav2011/><ref>{{cite book| vauthors = Sneader W |title=Drug Discovery: a History |date=2005 |publisher=Wiley |location=Chichester|isbn=9780471899792|page=349|edition=Rev. and updated|url=https://books.google.com/books?id=Cb6BOkj9fK4C&pg=PA349|url-status=live|archive-url=https://web.archive.org/web/20151226180447/https://books.google.ca/books?id=Cb6BOkj9fK4C&pg=PA349|archive-date=2015-12-26}}</ref> Ergometrine is regulated because it can be used to make [[lysergic acid diethylamide]] (LSD).<ref>{{cite book| vauthors = King LA |title=Forensic chemistry of substance misuse : a guide to drug control|date=2009|publisher=Royal Society of Chemistry|location=Cambridge, UK|isbn=9780854041787|page=190|url=https://books.google.com/books?id=x9Z1QZ5NIEIC&pg=PA190|url-status=live|archive-url=https://web.archive.org/web/20151226165636/https://books.google.ca/books?id=x9Z1QZ5NIEIC&pg=PA190|archive-date=2015-12-26}}</ref>

<!-- Society and culture -->

Ergometrine was discovered in 1932.<ref name=Rav2011>{{cite book| vauthors = Ravina E |title=The evolution of drug discovery : from traditional medicines to modern drugs|date=2011|publisher=Wiley-VCH|location=Weinheim|isbn=9783527326693|page=245|edition= 1st |url=https://books.google.com/books?id=iDNy0XxGqT8C&pg=PA245|url-status=live|archive-url=https://web.archive.org/web/20151226162800/https://books.google.ca/books?id=iDNy0XxGqT8C&pg=PA245|archive-date=2015-12-26}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref><ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref>

==Medical uses==

Ergometrine has a medical use in [[obstetrics]] to facilitate delivery of the [[placenta]] and to prevent [[bleeding]] after [[childbirth]] by causing [[smooth muscle]] tissue in the [[blood vessel]] walls to narrow, thereby reducing blood flow. It is usually combined with [[oxytocin]] (Syntocinon) as [[syntometrine]].

It can induce spasm of the [[coronary arteries]].<ref name="pmid16162623">{{cite journal | vauthors = Romagnoli E, Niccoli G, Crea F | title = Images in cardiology: A coronary organic stenosis distal to severe, ergonovine induced spasm: decision making | journal = Heart | volume = 91 | issue = 10 | pages = 1310 | date = October 2005 | pmid = 16162623 | pmc = 1769140 | doi = 10.1136/hrt.2004.058560 }}</ref> It is used to diagnose [[Prinzmetal's angina|variant (Prinzmetal's) angina]].<ref name="pmid10987346">{{cite journal | vauthors = Sunagawa O, Shinzato Y, Touma T, Tomori M, Fukiyama K | title = Differences between coronary hyperresponsiveness to ergonovine and vasospastic angina | journal = Japanese Heart Journal | volume = 41 | issue = 3 | pages = 257–268 | date = May 2000 | pmid = 10987346 | doi = 10.1536/jhj.41.257 | doi-access = free }}</ref>

Possible side effects include [[nausea]], [[vomiting]], abdominal pain, [[diarrhea]], [[headache]], [[dizziness]], [[tinnitus]], [[chest pain]], [[palpitation]], [[bradycardia]], transient hypertension and other cardiac [[arrhythmias]], [[dyspnea]], [[rashes]], and [[Shock (circulatory)|shock]].<ref>{{cite web | url = http://www.drugsupdate.com/generic/view/138 | title = Ergometrine drug information | work = DrugsUpdate.com | archive-url = https://web.archive.org/web/20120425092448/http://www.drugsupdate.com/generic/view/138 | archive-date=2012-04-25 }}</ref> An overdose produces a characteristic poisoning, [[ergotism]] or "St. Anthony's fire": prolonged [[vasospasm]] resulting in [[gangrene]] and amputations; hallucinations and dementia; and abortions.

Gastrointestinal disturbances such as diarrhea, nausea, and vomiting, are common.<ref>{{cite journal | vauthors = McDonald S, Abbott JM, Higgins SP | title = Prophylactic ergometrine-oxytocin versus oxytocin for the third stage of labour | journal = The Cochrane Database of Systematic Reviews | volume = 2004 | issue = 1 | pages = CD000201 | date = 2004 | pmid = 14973949 | pmc = 6491201 | doi = 10.1002/14651858.CD000201.pub2 }}</ref> The drug is contraindicated in pregnancy, vascular disease, and psychosis.

==Pharmacology==

===Pharmacodynamics===

While ergometrine acts at [[alpha-adrenergic receptor|α-adrenergic]], [[dopamine receptor|dopaminergic]], and [[serotonin receptor]]s (the [[5-HT2 receptor|5-HT₂ receptor]]), it exerts on the [[uterus]] (and other [[smooth muscles]]) a powerful stimulant effect not clearly associated with a specific receptor type.{{cn|date=August 2020}}

Ergometrine produces [[psychedelic drug|psychedelic]] effects at high doses (e.g., 2–10&nbsp;mg; normal therapeutic doses are 0.2 to 0.4&nbsp;mg).<ref name="pmid7420432">{{cite journal | vauthors = Ott J, Neely P | title = Entheogenic (hallucinogenic) effects of methylergonovine | journal = Journal of Psychedelic Drugs | volume = 12 | issue = 2 | pages = 165–166 | date = 1980 | pmid = 7420432 | doi = 10.1080/02791072.1980.10471568 }}</ref> This can be attributed to activation of [[5-HT2A receptor|5-HT_2A receptor]]s.<ref name="HalberstadtNichols2020">{{cite book| vauthors = Halberstadt AL, Nichols DE |title=Handbook of the Behavioral Neurobiology of Serotonin|chapter=Serotonin and serotonin receptors in hallucinogen action|series=Handbook of Behavioral Neuroscience|volume=31|year=2020|pages=843–863|issn=1569-7339|doi=10.1016/B978-0-444-64125-0.00043-8|isbn=9780444641250|s2cid=241134396}}</ref> Ergometrine is an agonist of the serotonin [[5-HT2B receptor|5-HT_2B receptor]] and has been associated with [[cardiac valvulopathy]].<ref name="pmid24361689">{{cite journal | vauthors = Cavero I, Guillon JM | title = Safety Pharmacology assessment of drugs with biased 5-HT(2B) receptor agonism mediating cardiac valvulopathy | journal = Journal of Pharmacological and Toxicological Methods | volume = 69 | issue = 2 | pages = 150–161 | date = 2014 | pmid = 24361689 | doi = 10.1016/j.vascn.2013.12.004 }}</ref>

==History==

The pharmacological properties of ergot were known and had been utilised by midwives for centuries, but were not thoroughly researched and publicized until the early 20th century. However, its abortifacient effects and the danger of ergotism meant that it was only prescribed cautiously, as in the treatment of [[postpartum haemorrhage]].<ref name="decosta">{{cite journal | vauthors = De Costa C | title = St Anthony's fire and living ligatures: a short history of ergometrine | journal = Lancet | volume = 359 | issue = 9319 | pages = 1768–1770 | date = May 2002 | pmid = 12049883 | doi = 10.1016/S0140-6736(02)08658-0 | s2cid = 53277037 }}<!--|access-date=3 December 2014--></ref>

Ergometrine was first isolated and obtained by the chemists [[Chassar Moir|C Moir]], H W Dudley and Gerald Rogers{{fact|date=July 2021}} in 1935.<ref>{{cite journal | vauthors = Dudley HW, Moir C | title = The Substance Responsible for the Traditional Clinical Effect of Ergot | journal = British Medical Journal | volume = 1 | issue = 3871 | pages = 520–523 | date = March 1935 | pmid = 20778930 | pmc = 2459740 | doi = 10.1136/bmj.1.3871.520 }}<!--|access-date=3 December 2014--></ref><ref name="pmid32805212">{{cite journal | vauthors = Hoyer D | title = Targeting the 5-HT system: Potential side effects | journal = Neuropharmacology | volume = 179 | issue = | pages = 108233 | date = November 2020 | pmid = 32805212 | doi = 10.1016/j.neuropharm.2020.108233 | s2cid = 221118172 }}</ref> Caroline De Costa has argued that the adoption of ergometrine for [[prophylactic|preventive]] use and for treating bleeding contributed to the decline in the [[maternal mortality rate]] in much of the West during the early 20th century.<ref name="decosta" />

==Society and culture==

===Legal status===

Ergometrine is listed as Table I precursors under the [[United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances]], as possible precursor compound for LSD.<ref>{{cite web | publisher = International Narcotics Control Board | location = Vienna, Austria | edition = Eleventh | date = January 2007 | url = http://www.incb.org/pdf/e/list/red.pdf | title = List of Precursors and Chemicals Frequently Used in the Illicit Manufacture of Narcotic Drugs and Psychotropic Substances Under International Control | archive-url = https://web.archive.org/web/20080227224025/http://www.incb.org/pdf/e/list/red.pdf | archive-date=February 27, 2008 }}</ref> As an N-alkyl derivative of lysergamide, ergometrine is also covered by the [[Misuse of Drugs Act 1971]], effectively rendering it illegal in the [[United Kingdom]].

== References ==

{{Reflist}}

== External links ==

* {{cite web|url=https://cytotecperu-lima.com/que-es-ergotrate.html|publisher=U.S. National Library of Medicine|work=Drug Information Portal|title=Ergotrate|date=15 November 2018}}

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