Ergometrine

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 heavy vaginal bleeding after childbirth.[3][1] It can be used either by mouth, by injection into a muscle, or injection into a vein.[3] It begins working within 15 minutes when taken by mouth and is faster in onset when used by injection.[3] Effects last between 45 and 180 minutes.[3]

Ergometrine
Clinical data
Trade namesErgometrine Maleate, Ergonovine Maleate, Ergotrate, Ergotrate Maleate, Ergostat, Syntometrine, others[1][2]
Other namesErgonovine; d-Lysergic acid β-propanolamide
AHFS/Drugs.comMonograph
Pregnancy
category
  • X
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
MetabolismLiver (partly CYP3A4)
Elimination half-life2-phase (10 min; 2 hrs)
ExcretionBiliary
Identifiers
IUPAC name
  • (6aR,9R)-N-((S)-1-Hydroxypropan- 2-yl)-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.441
Chemical and physical data
FormulaC19H23N3O2
Molar mass325.412 g·mol−1
3D model (JSmol)
SMILES
  • [H][C@@]12Cc3c[nH]c4cccc(C1=C[C@@H](C(=O)N[C@@H](C)CO)CN2C)c34
InChI
  • InChI=1S/C19H23N3O2/c1-11(10-23)21-19(24)13-6-15-14-4-3-5-16-18(14)12(8-20-16)7-17(15)22(2)9-13/h3-6,8,11,13,17,20,23H,7,9-10H2,1-2H3,(H,21,24)/t11-,13+,17+/m0/s1 Y
  • Key:WVVSZNPYNCNODU-XTQGRXLLSA-N Y
  (verify)

Common side effect include high blood pressure, vomiting, seizures, headache, and low blood pressure.[3] Other serious side effects include ergotism.[3] It was originally made from the rye ergot fungus but can also be made from lysergic acid.[4][5] Ergometrine is regulated because it can be used to make lysergic acid diethylamide (LSD).[6]

Ergometrine was discovered in 1932.[4] It is on the World Health Organization's List of Essential Medicines.[7][8]

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.[9] It is used to diagnose variant (Prinzmetal's) angina.[10]

Side effects

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.[11] 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.[12] The drug is contraindicated in pregnancy, vascular disease, and psychosis.

Pharmacology

Pharmacodynamics

While ergometrine acts at α-adrenergic, dopaminergic, and serotonin receptors (the 5-HT2 receptor), it exerts on the uterus (and other smooth muscles) a powerful stimulant effect not clearly associated with a specific receptor type.

Ergometrine produces psychedelic effects at high doses (e.g., 2–10 mg; normal therapeutic doses are 0.2 to 0.4 mg).[13] This can be attributed to activation of 5-HT2A receptors.[14] Ergometrine is an agonist of the serotonin 5-HT2B receptor and has been associated with cardiac valvulopathy.[15]

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.[16]

Ergometrine was first isolated and obtained by the chemists C Moir, H W Dudley and Gerald Rogers in 1935.[17][18] Caroline De Costa has argued that the adoption of ergometrine for preventative use and for treating bleeding contributed to the decline in the maternal mortality rate in much of the West during the early 20th century.[16]

Society and culture

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.[19] 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
  1. I.K. Morton; Judith M. Hall (31 October 1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 113–. ISBN 978-0-7514-0499-9.
  2. Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 397–. ISBN 978-3-88763-075-1.
  3. "Ergonovine Maleate". The American Society of Health-System Pharmacists. Archived from the original on 2015-12-25. Retrieved 1 December 2015.
  4. Ravina, Enrique (2011). The evolution of drug discovery : from traditional medicines to modern drugs (1. Aufl. ed.). Weinheim: Wiley-VCH. p. 245. ISBN 9783527326693. Archived from the original on 2015-12-26.
  5. Sneader, Walter (2005). Drug discovery : a history (Rev. and updated ed.). Chichester: Wiley. p. 349. ISBN 9780471899792. Archived from the original on 2015-12-26.
  6. King, L.A. (2009). Forensic chemistry of substance misuse : a guide to drug control. Cambridge, UK: Royal Society of Chemistry. p. 190. ISBN 9780854041787. Archived from the original on 2015-12-26.
  7. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  8. World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
  9. Romagnoli E, Niccoli G, Crea F (October 2005). "Images in cardiology: A coronary organic stenosis distal to severe, ergonovine induced spasm: decision making". Heart. 91 (10): 1310. doi:10.1136/hrt.2004.058560. PMC 1769140. PMID 16162623.
  10. Sunagawa O, Shinzato Y, Touma T, Tomori M, Fukiyama K (May 2000). "Differences between coronary hyperresponsiveness to ergonovine and vasospastic angina". Jpn Heart J. 41 (3): 257–68. doi:10.1536/jhj.41.257. PMID 10987346.
  11. Ergometrine drug information Archived 2012-04-25 at the Wayback Machine
  12. McDonald S, Abbott JM, Higgins SP (2004). "Prophylactic ergometrine-oxytocin versus oxytocin for the third stage of labour". Cochrane Database Syst Rev. 1 (1): CD000201. doi:10.1002/14651858.CD000201.pub2. PMC 6491201. PMID 14973949.
  13. Ott J, Neely P (1980). "Entheogenic (hallucinogenic) effects of methylergonovine". J Psychedelic Drugs. 12 (2): 165–6. doi:10.1080/02791072.1980.10471568. PMID 7420432.
  14. Halberstadt, Adam L.; Nichols, David E. (2020). "Serotonin and serotonin receptors in hallucinogen action". Handbook of the Behavioral Neurobiology of Serotonin. Handbook of Behavioral Neuroscience. Vol. 31. pp. 843–863. doi:10.1016/B978-0-444-64125-0.00043-8. ISBN 9780444641250. ISSN 1569-7339. S2CID 241134396.
  15. Cavero I, Guillon JM (2014). "Safety Pharmacology assessment of drugs with biased 5-HT(2B) receptor agonism mediating cardiac valvulopathy". J Pharmacol Toxicol Methods. 69 (2): 150–61. doi:10.1016/j.vascn.2013.12.004. PMID 24361689.
  16. De Costa, Caroline (May 2002). "St Anthony's fire and living ligatures: a short history of ergometrine". Lancet. 359 (9319): 1768–1770. doi:10.1016/S0140-6736(02)08658-0. PMID 12049883.
  17. Dudley, H W; Moir, C (1935). "The substance responsible for the traditional clinical effect of ergot". BMJ. 1 (3871): 520–523. doi:10.1136/bmj.1.3871.520. PMC 2459740. PMID 20778930.
  18. Hoyer D (November 2020). "Targeting the 5-HT system: Potential side effects". Neuropharmacology. 179: 108233. doi:10.1016/j.neuropharm.2020.108233. PMID 32805212. S2CID 221118172.
  19. List Of Precursors And Chemicals Frequently Used In The Illicit Manufacture Of Narcotic Drugs And Psychotropic Substances Under International Control Archived February 27, 2008, at the Wayback Machine.
  • "Ergotrate". Drug Information Portal. U.S. National Library of Medicine. 15 November 2018.


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