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Ergometrine

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Ergometrine
Clinical data
Trade namesErgometrine Maleate, Ergonovine Maleate, Ergotrate, Ergotrate Maleate, Ergostat, Syntometrine, others[1][2]
Other namesergonovine[3]; ᴅ-lysergic acid β-propanolamide[4]; ᴅ-lysergic acid α-hydroxymethylethylamide[4]; ᴅ-(+)-lysergic acid-β-hydroxyisopropylamide[4]
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
  • (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 Edit this at Wikidata
Chemical and physical data
FormulaC19H23N3O2
Molar mass325.412 g·mol−1
3D model (JSmol)
  • [H][C@@]12Cc3c[nH]c4cccc(C1=C[C@@H](C(=O)N[C@@H](C)CO)CN2C)c34
  • 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 checkY
  • Key:WVVSZNPYNCNODU-XTQGRXLLSA-N checkY
  (verify)

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.[6][1] It can be used either by mouth, by injection into a muscle, or injection into a vein.[6] It begins working within 15 minutes when taken by mouth and is faster in onset when used by injection.[6] Effects last between 45 and 180 minutes.[6]

Common side effect include high blood pressure, vomiting, seizures, headache, and low blood pressure.[6] Other serious side effects include ergotism.[6] It was originally made from the rye ergot fungus but can also be made from lysergic acid.[7][8] Ergometrine is regulated because it can be used to make lysergic acid diethylamide (LSD).[9]

Ergometrine was discovered in 1932.[7] It is on the World Health Organization's List of Essential Medicines.[10][11]

Medical uses

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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.[12] It is used to diagnose variant (Prinzmetal's) angina.[13]

Side effects

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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.[14] 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.[15] The drug is contraindicated in pregnancy, vascular disease, and psychosis.

Pharmacology

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Pharmacodynamics

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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 produces psychedelic effects at high doses (e.g., 2–10 mg; normal therapeutic doses are 0.2 to 0.4 mg).[16] This can be attributed to activation of 5-HT2A receptors.[17] Ergometrine is an agonist of the serotonin 5-HT2B receptor and has been associated with cardiac valvulopathy.[18]

Psychedelic Effects

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The psychoactive property of these simple lysergic acid amides, closely related to LSD, is well established. The question presented itself whether ergonovine, being not only an alkaloidal component of ergot but also of ololiuhqui, possessed hallucinogenic activ­ity. In the light of its chemical structure this did not seem unlikely: it does not differ much from LSD. But one may ask why, if it is hallucinogenic, this astonishing fact has not been announced, in the light ofits use over recent decades in obstetrics. Undoubted­ly the answer lies in the extremely low dosage of ergonovine used to stop postpartum bleeding, viz 0.1 to 0.25 mg. The effective dose of lysergic acid amide is 1to 2 mg by oral application. I decided therefore to test in a self-experiment a corresponding dose of ergonovine:

1 April 1976

12.20 h: 2.0 mg ergonovine hydrogenmaleinate, containing 1.5 mg ergonovine base, ingested in a glass of water.
13.00 h: slight nausea, same effect as I have experienced always in my LSD or psilocybin experiments. Tired, need to lie down. With eyes closed colored figures.
13.30 h: the trees in the nearby forest seem to live, their branches moving in a threatening way.
14.30 h: strong desire to dream, unable to do systematic work, with eyes closed or open afflicted by mollusk-like forms and feelings.
16.00 h: motives and colors have become clearer, but bearing still some hidden dangers.
17.00 h: after a short sleep I awoke by a kind of inner explosion of all the senses.
18.00 h: an unexpected visit forced me to become active, but during the whole evening I lived more in an inner than in the outer world.
22.00 h: all effects worn off, normal feeling.

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.

Albert Hofmann in The Road to Eleusis[19]

In 1937, Albert Hofmann of Sandoz, a Swiss pharmaceutical firm, was the first to succeed in the synthesis of an ergot alkaloidmore specifically, ergonovinefrom lysergic acid and propanolamine, obtaining a chemical structure of d-lysergic acid, L-2-propanolamide. This achievement opened up the way to wider, commercial, therapeutic uses of this substance in a maleate form. In 1977 and 1978, Hofmann reported that ergonovine maleate possessed entheogenic properties, a fact that should not be too surprising, since ergot had been an important contingency to the experience of divine epiphanies in sacred religious mysteries, as those of Demeter and Dionysos. While in Greece working on sections of this book, I had the opportunity to duplicate Hofmann's experiment with ergonovine maleate, in a controlled environment. The objective was to find out the entheogenic characteristics of this alkaloid. Each one of us ingested 6.0 mg. of the substance dissolved in a little water, three times the dosage taken by Hofmann and his colleagues. 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. This may be ascribed to the fact that ergonovine is only one of the psychoactive alkaloids present in ergot. In antiquity, the entire mass of the ergot was used in the preparation of the hallucinogenic potion, in which the combined actions of ergonovine and ergine could enhance the potency of each other and produce a considerably more powerful effect.

Michael Ripinsky-Naxon[20]

History

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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.[21]

Ergometrine was first isolated and obtained by the chemists C Moir, H W Dudley and Gerald Rogers[citation needed] in 1935.[22][23] 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.[21]

Society and culture

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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.[24] 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

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  1. ^ a b 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). Vienna International Centre, P.O. Box 500, 1400 Vienna, Austria: International Narcotics Control Board. p. 11. Retrieved 2024-11-17.{{cite book}}: CS1 maint: location (link)
  4. ^ a b c International Narcotics Control Board Red List, 17ᵗʰ edition, January 2020 (PDF). Vienna International Centre, P.O. Box 500, 1400 Vienna, Austria: International Narcotics Control Board. p. 13. Retrieved 2024-11-17.{{cite book}}: CS1 maint: location (link)
  5. ^ 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.
  6. ^ a b c d e f "Ergonovine Maleate". The American Society of Health-System Pharmacists. Archived from the original on 2015-12-25. Retrieved 1 December 2015.
  7. ^ a b 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ "Ergometrine drug information". DrugsUpdate.com. Archived from the original on 2012-04-25.
  15. ^ 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.
  16. ^ Ott J, Neely P (1980). "Entheogenic (hallucinogenic) effects of methylergonovine". Journal of Psychedelic Drugs. 12 (2): 165–166. doi:10.1080/02791072.1980.10471568. PMID 7420432.
  17. ^ 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.
  18. ^ 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.
  19. ^ Wasson, R. G.; Hofmann, Albert; Ruck, Carl A. P.; Webster, Peter (1978 (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. {{cite book}}: Check date values in: |year= (help)CS1 maint: year (link)
  20. ^ Ripinsky-Naxon, Michael (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.
  21. ^ a b 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.
  22. ^ 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.
  23. ^ 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.
  24. ^ "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.
[edit]
  • "Ergotrate". Drug Information Portal. U.S. National Library of Medicine. 15 November 2018.
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