Ergonovine

Ergonovine
Clinical data
Trade namesErgotrate, Ergotrate Maleate, Ergostat, Syntometrine[1][2]
Other namesergometrine[3][4] ergobasin[3] ergotocine[3] ergostetrine[3] ᴅ-lysergic acid-1,2-propanolamide[4] ᴅ-lysergic acid 1-(hydroxymethyl)ethylamide[4] ᴅ(+)-lysergic acid-β-hydroxyisopropylamide[4]
AHFS/Drugs.comMonograph
Pregnancy
category
  • X
Routes of
administration		oral, injection
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)

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vomiting, seizures, headache, and low blood pressure.[6] Other serious side effects include ergotism.[6] It was originally made from the rye ergot fungus but can also be made from lysergic acid.[7][8] Ergonovine is regulated because it can be used to make lysergic acid diethylamide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

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

Medical uses

Ergonovine 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

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

Pharmacodynamics

Ergonovine stimulates the uterus and other smooth muscles. It tragets α-adrenergic, dopaminergic, and serotonin receptors (the 5-HT2 receptor). Its uterotonic effect has not been identified with a specific receptor type.[citation needed] Ergonovine is an agonist of the serotonin 5-HT2B receptor and has been associated with cardiac valvulopathy.[16]

Psychedelic Effects

Ergonovine induces psychedelic effects at doses of 2–10mg, in contrast to its medical use in doses of 0.2–0.4mg.[17][18][19][20][21] The most common source of ergonovine for drug users is Ipomoea tricolor seeds, as they are the only commonly available natural product that hosts an ergoline-generating fungus.[22] The ergonovine content of I. tricolor seeds varies between one-tenth and one-third of ergine, an ergonovine analog.[23] One person who had the opportunity to try ergonovine to see its psychedelic potential stated that it was mild relative to other psychedelics, but that ergine may synergize with it;[24] indeed the contrast between Hofmann's self-administration of Ipomoea corymbosa extract and synthetic ergine is apparent in his essay on the initial analysis of I. corymbosa and I. tricolor seeds.[25]

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 of its 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 1 to 2 mg by oral application. I decided therefore to test in a self-experiment a corresponding dose of ergonovine:

–Albert Hofmann[17]

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.[26]

Ergonovine was first isolated and obtained by the chemists C Moir, H W Dudley and Gerald Rogers[citation needed] in 1935.[27][28] Caroline De Costa has argued that the adoption of ergonovine 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.[26]

Society and culture

Ergonovine 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.[29] As an N-alkyl derivative of ergine, ergonovine is also covered by the Misuse of Drugs Act 1971, effectively rendering it illegal in the United Kingdom.

References

  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. ^ a b c d Wasson RG, Hofmann A, Ruck CA, Webster P (2008-11-25) [1978]. The Road to Eleusis: Unveiling the Secret of the Mysteries. Berkley, California: North Atlantic Books. p. 38. ISBN 9781556437526.
  4. ^ a b c d 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. ergometrine is on p. 11, the other three are on p. 13.
  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. ^ 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.
  17. ^ a b Wasson RG, Hofmann A, Ruck CA, Webster P (2008-11-25) [1978]. "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 9781556437526.
  18. ^ 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.
  19. ^ 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.
  20. ^ Eisner B (January 10, 2004). "Interview with an Alchemist: Bear Owsley Interview". Bruce Eisner's Writings. Archived from the original on 29 September 2004. Retrieved 2024-11-18.
  21. ^ Connie Littlefield (2002). Hofmann's Potion. Conceptafilm.
  22. ^ Leistner E, Steiner U (February 3, 2018). "The Genus Periglandula and Its Symbiotum with Morning Glory Plants (Convolvulaceae)". In Anke T, Schüffler A (eds.). Physiology and Genetics. Cham: Springer International Publishing. pp. 131–147. doi:10.1007/978-3-319-71740-1_5. ISBN 978-3-319-71739-5. Retrieved 2024-11-21.
  23. ^ Nowak J, Woźniakiewicz M, Klepacki P, Sowa A, Kościelniak P (May 2016). "Identification and determination of ergot alkaloids in Morning Glory cultivars". Analytical and Bioanalytical Chemistry. 408 (12) (published February 14, 2016): 3093–3102. doi:10.1007/s00216-016-9322-5. PMC 4830885. PMID 26873205.
  24. ^ 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.
  25. ^ Hofmann A (1963). "The Active Principles of the Seeds of Rivea corymbosa and Ipomoea violacea". Harvard Botanical Museum Leaflets. 20 (6). Harvard University Herbaria: 194-212 (19 pgs.).
  26. ^ 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.
  27. ^ 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.
  28. ^ 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.
  29. ^ "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.
  • "Ergotrate". Drug Information Portal. U.S. National Library of Medicine. 15 November 2018.