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.^[5][1] It can be used either by mouth, by injection into a muscle, or injection into a vein.^[5] It begins working within 15 minutes when taken by mouth and is faster in onset when used by injection.^[5] Effects last between 45 and 180 minutes.^[5]

Ergometrine

Clinical data
Trade names	Ergometrine Maleate, Ergonovine Maleate, Ergotrate, Ergotrate Maleate, Ergostat, Syntometrine, others[1][2]
Other names	ergonovine[3] ᴅ-lysergic acid-1,2-propanolamide[3] ᴅ-lysergic acid 1-(hydroxymethyl)ethylamide[3] ᴅ(+)-lysergic acid-β-hydroxyisopropylamide[3]
AHFS/Drugs.com	Monograph
Pregnancy category	X
Routes of administration	By mouth
ATC code	G02AB03 (WHO)
Legal status
Legal status	BR: Class D1 (Drug precursors)[4] CA: Schedule VI US: ℞-only
Pharmacokinetic data
Metabolism	Liver (partly CYP3A4)
Elimination half-life	2-phase (10 min; 2 hrs)
Excretion	Biliary
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	60-79-7 Y
PubChem CID	443884
IUPHAR/BPS	148
DrugBank	DB01253 Y
ChemSpider	391970 Y
UNII	WH41D8433D
KEGG	D07905 Y
ChEBI	CHEBI:4822 Y
ChEMBL	ChEMBL119443 Y
CompTox Dashboard (EPA)	DTXSID8046323
ECHA InfoCard	100.000.441
Chemical and physical data
Formula	C19H23N3O2
Molar mass	325.412 g·mol−1
3D model (JSmol)	Interactive image
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vomiting, seizures, headache, and low blood pressure.^[5] Other serious side effects include ergotism.^[5] It was originally made from the rye ergot fungus but can also be made from lysergic acid.^[6][7] Ergometrine is regulated because it can be used to make lysergic acid diethylamide (LSD).^[8]

Ergometrine was discovered in 1932.^[6] It is on the World Health Organization's List of Essential Medicines.^[9][10]

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.^[11] It is used to diagnose variant (Prinzmetal's) angina.^[12]

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.^[13] 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.^[14] 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.^{[citation needed]}

Ergometrine induces psychedelic effects at high doses (e.g., 2–10 mg; normal therapeutic doses are 0.2 to 0.4 mg).^{[15][16][17][18][19]} This can be attributed to activation of 5-HT_2A receptors^[20] and its structure (“it does not differ much from LSD.” -Albert Hofmann^[15]). Ergometrine is an agonist of the serotonin 5-HT_2B receptor and has been associated with cardiac valvulopathy.^[21]

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.^[22]

Ergometrine was first isolated and obtained by the chemists C Moir, H W Dudley and Gerald Rogers^{[citation needed]} in 1935.^[23][24] Caroline De Costa has argued that the adoption of ergometrine for 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.^[22]

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.^[25] 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. Morton IK, Hall JM (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. International Narcotics Control Board Red List, 17ᵗʰ edition, January 2020 (PDF) (Report). Vienna International Centre, Vienna, Austria: International Narcotics Control Board. Retrieved 2024-11-17. [ergonovine is on p. 11, the other three are on p. 13.]
4. Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-15.
5. "Ergonovine Maleate". The American Society of Health-System Pharmacists. Archived from the original on 2015-12-25. Retrieved 1 December 2015.
6. Ravina E (2011). The evolution of drug discovery : from traditional medicines to modern drugs (1st ed.). Weinheim: Wiley-VCH. p. 245. ISBN 9783527326693. Archived from the original on 2015-12-26.
7. Sneader W (2005). Drug Discovery: a History (Rev. and updated ed.). Chichester: Wiley. p. 349. ISBN 9780471899792. Archived from the original on 2015-12-26.
8. King LA (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.
9. 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.
10. 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.
11. 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.
12. Sunagawa O, Shinzato Y, Touma T, Tomori M, Fukiyama K (May 2000). "Differences between coronary hyperresponsiveness to ergonovine and vasospastic angina". Japanese Heart Journal. 41 (3): 257–268. doi:10.1536/jhj.41.257. PMID 10987346.
13. "Ergometrine drug information". DrugsUpdate.com. Archived from the original on 2012-04-25.
14. McDonald S, Abbott JM, Higgins SP (2004). "Prophylactic ergometrine-oxytocin versus oxytocin for the third stage of labour". The Cochrane Database of Systematic Reviews. 2004 (1): CD000201. doi:10.1002/14651858.CD000201.pub2. PMC 6491201. PMID 14973949.
15. Wasson RG, Hofmann A, Ruck CA, Webster P (2023). "Chapter 2, A Challenging Question and My Answer (Hofmann)". The Road to Eleusis: Unveiling the Secret of the Mysteries. Berkley, California: North Atlantic Books. pp. 39–41. ISBN 9781623177768. “This was an experiment performed without attention to “set and setting” but it proves that ergonovine possesses a psychotropic, mood-changing, slightly hallucinogenic activity when taken in the same amount [as an] effective dose of lysergic acid amide, the main constituent of ololiuhqui. Its potency is about one twentieth of the potency of LSD and about five times that of psilocybin.” (p. 41)
16. Bigwood J, Ott J, Thompson C, Neely P (1979). "Entheogenic effects of ergonovine". Journal of Psychedelic Drugs. 11 (1–2): 147–149. doi:10.1080/02791072.1979.10472099. PMID 522166. “The mild entheogenic effects of ergonovine are similar to those of LSD. However, in dramatic contrast to LSD, the somatic effects of ergonovine greatly overshadow its psychic effects, so much so that we had no wish to ingest more than 10.0 mg,” (p. 148)
17. Ripinsky-Naxon M (1993). "Chapter 5, The Ritual Drug Complex: Ethnobiology of Heaven and Hell. Psychoactivity and Mechanisms of Hallucinations". The Nature of Shamanism: Substance and Function of a Religious Metaphor. Albany, NY: State University of New York Press. p. 146. ISBN 9781438417417. “We experienced low intensity perceptual alterations, if one might call it so, of the surroundings, both natural and man-made, characterized by a sense of spiritual profoundness imbedded in outdoor nature. There was a mild awareness of inner personal spirituality and insight (entheoi), without hallucination or euphoria. The somatic effects consisted primarily of mild leg cramps. As an entheogen, on the whole, ergonovine maleate did not prove so impressive as, for instance, LSD or psilocybin.”
18. Eisner B (January 10, 2004). "Interview with an Alchemist: Bear Owsley Interview". Bruce Eisner's Writings. Retrieved 2024-11-18. “[Isoergine] is one of them; hydroxy-methyl-lysergamide is another one, and in fact, is considered nearly identical to LSD in effect. Albert [Hofmann] told me so himself.” (Owsley Stanley) [“Hydroxy-methyl-lysergamide” is a reference to one of ergonovine’s synonyms; see “Other names” in the infobox at the top of the page.]
19. Connie Littlefield (2002). Hofmann’s Potion. Conceptafilm. Retrieved 2024-11-18. “When I discovered LSD, it was believed it was a product of laboratory. And then we discovered that this compound had existed already for thousands of years in the plant kingdom...not exactly LSD, but practically.” (Albert Hofmann, 4 min. 53 sec.) [It isn’t known if this is a reference to ergonovine, ergine, or both.]
20. Halberstadt AL, Nichols DE (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.
21. Cavero I, Guillon JM (2014). "Safety Pharmacology assessment of drugs with biased 5-HT(2B) receptor agonism mediating cardiac valvulopathy". Journal of Pharmacological and Toxicological Methods. 69 (2): 150–161. doi:10.1016/j.vascn.2013.12.004. PMID 24361689.
22. De Costa C (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. S2CID 53277037.
23. Dudley HW, Moir C (March 1935). "The Substance Responsible for the Traditional Clinical Effect of Ergot". British Medical Journal. 1 (3871): 520–523. doi:10.1136/bmj.1.3871.520. PMC 2459740. PMID 20778930.
24. 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.
25. "List of Precursors and Chemicals Frequently Used in the Illicit Manufacture of Narcotic Drugs and Psychotropic Substances Under International Control" (PDF) (Eleventh ed.). Vienna, Austria: International Narcotics Control Board. January 2007. Archived from the original (PDF) on February 27, 2008.

External links

• "Ergotrate". Drug Information Portal. U.S. National Library of Medicine. 15 November 2018.