Ergometrine

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Ergometrine
Ergonovine-skeletal.svg Ergometrine3.png
Systematic (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
Clinical data
AHFS/Drugs.com monograph
Pregnancy cat.
  • X
Legal status
  • List I precursor (US)
Routes Oral
Pharmacokinetic data
Metabolism hepatic
Excretion renal
Identifiers
CAS number 60-79-7 YesY
ATC code G02AB03
PubChem CID 443884
DrugBank DB01253
ChemSpider 391970 YesY
UNII WH41D8433D YesY
KEGG D07905 YesY
ChEBI CHEBI:4822 YesY
ChEMBL CHEMBL119443 YesY
Synonyms Ergonovine, lysergic acid beta- propanolamide
Chemical data
Formula C19H23N3O2 
Mol. mass 325.41 g/mol
 YesY (what is this?)  (verify)

Ergometrine (other names include ergonovine and d-lysergic acid beta-propanolamide), is an ergoline (and lysergamide) derivative, and one of the primary ergot and morning glory alkaloids. It is chemically similar to lysergic acid diethylamide (LSD), ergine, and lysergic acid.

It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.[1]

Medical use[edit]

It 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.[2] It is used to diagnose variant (Prinzmetal's) angina.[3]

Side effects[edit]

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.[4] 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.[5] The drug is contraindicated in pregnancy, vascular disease, and psychosis.

Mechanism of action[edit]

While it acts at alpha-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.

History[edit]

The pharmacological properties of ergot were known and had been utilised by midwives for centuries, but were not thoroughly researched and publicised 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.[6]

Ergometrine was first isolated and obtained by the chemists C Moir and H W Dudley in 1935.[7] Caroline De Costa has argued that the adoption of ergometrine for prophylatic use and for treating haemorrhaging contributed to the decline in the maternal mortality rate in much of the West during the early 20th century.[6]

Legal status[edit]

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.[8] 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.

Chemistry[edit]

Ergometrine can be synthesized by esterification of D-lysergic acid using 2-aminopropanol in dimethylformamide and direct treatment of the reaction mixture with phosgene.[9]

Ergonovine synthesis.png

References[edit]

  1. ^ "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ Ergometrine drug information
  5. ^ McDonald S, Abbott JM, Higgins SP (2004). "Prophylactic ergometrine-oxytocin versus oxytocin for the third stage of labour". Cochrane Database Syst Rev 1: CD000201. doi:10.1002/14651858.CD000201.pub2. PMID 14973949. 
  6. ^ a b 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. 
  7. ^ Dudley, H W; Moir, C (1935). "The substance responsible for the traditional clinical effect of ergot". BMJ 1: 520–523. 
  8. ^ List Of Precursors And Chemicals Frequently Used In The Illicit Manufacture Of Narcotic Drugs And Psychotropic Substances Under International Control.
  9. ^ A. Stoll, A. Hofmann, Helv. Chim. Acta, 26, 956 (1943).