Chemistry:Ergonovine

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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.[1][2] It can be used either by mouth, by injection into a muscle, or injection into a vein.[1]

Common side effects include high blood pressure, vomiting, seizures, headache, and low blood pressure.[1] Other serious side effects include ergotism.[1]

Ergonovine was discovered in 1932.[3] It is on the World Health Organization's List of Essential Medicines.[4] Ergonovine is controlled in some countries because it can be used to make the psychedelic drug lysergic acid diethylamide (LSD).[5] It is also known to produce psychedelic effects itself at high doses.[6][7]

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 begins working within 15 minutes when taken by mouth and is faster in onset when used by injection.[1] Its duration is between 45 and 180 minutes.[1]

It can induce spasm of the coronary arteries.[8] It is used to diagnose variant (Prinzmetal's) angina.[9]

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.[10] 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.[11] The drug is contraindicated in pregnancy, vascular disease, and psychosis.

Interactions

Pharmacology

Pharmacodynamics

Ergonovine stimulates the uterus and other smooth muscles. It targets α-adrenergic, dopaminergic, and serotonin receptors (the 5-HT2 receptor). Its uterotonic effect has not been identified with a specific receptor type.[citation needed] The drug has been found to bind to and activate the rat and human serotonin 5-HT2A receptor with similar affinity as lysergic acid diethylamide (LSD).[12][13] Ergonovine is an agonist of the serotonin 5-HT2B receptor and has been associated with cardiac valvulopathy.[14][13] A computer-predicted binding profile of ergonovine at an array of serotonin, dopamine, and other receptors has been published.[15] It was predicted to bind to most of the serotonin receptors with moderately high affinity, albeit lower than LSD.[15]

Chemistry

Synthesis

Ergonovine was originally made from the rye ergot fungus but can also be made from lysergic acid.[3][16]

Analogues

A simplified analogue of ergonovine that was also investigated as an oxytocic is tochergamine.

Natural occurrence

According to Albert Hofmann and other researchers, although ergonovine is naturally occurring in morning glory seeds and is known to produce psychedelic effects at higher doses,[7][17] it is present in too small of amounts to contribute to their psychoactive or hallucinogenic effects.[18][19][20][21]

History

The pharmacological properties of ergot were known and had been utilized 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]

Ergonovine 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 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.[22]

Society and culture

Recreational use

Ergonovine induces psychedelic effects at doses of 2–10 mg, in contrast to its medical use in doses of 0.2–0.4 mg.[6][7][25][26][27] 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.[28] The ergonovine content of I. tricolor seeds varies between one-tenth and one-third of ergine, an ergonovine analog.[29] 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;[30] 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.[31][6]

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 [...]

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.[32] 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.[citation needed]

See also

  • Substituted lysergamide

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 "Ergonovine Maleate". The American Society of Health-System Pharmacists. https://www.drugs.com/monograph/ergonovine-maleate.html. 
  2. ↑ Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. 31 October 1999. pp. 113–. ISBN 978-0-7514-0499-9. https://books.google.com/books?id=mqaOMOtk61IC&pg=PA113. 
  3. ↑ 3.0 3.1 The evolution of drug discovery: from traditional medicines to modern drugs (1st ed.). Weinheim: Wiley-VCH. 2011. p. 245. ISBN 978-3-527-32669-3. https://books.google.com/books?id=iDNy0XxGqT8C&pg=PA245. 
  4. ↑ World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. 2019. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO. 
  5. ↑ Forensic chemistry of substance misuse: a guide to drug control. Cambridge, UK: Royal Society of Chemistry. 2009. p. 190. ISBN 978-0-85404-178-7. https://books.google.com/books?id=x9Z1QZ5NIEIC&pg=PA190. 
  6. ↑ 6.0 6.1 6.2 "Chapter 2, A Challenging Question and My Answer (Hofmann)". The Road to Eleusis: Unveiling the Secret of the Mysteries. Berkley, California: North Atlantic Books. 2008-11-25. pp. 39–41. ISBN 978-1-55643-752-6. https://books.google.com/books?id=7JC7EAAAQBAJ&pg=PA39. 
  7. ↑ 7.0 7.1 7.2 "Entheogenic effects of ergonovine". J Psychedelic Drugs 11 (1–2): 147–149. 1979. doi:10.1080/02791072.1979.10472099. PMID 522166. https://bibliography.maps.org/resources/download/12845. Retrieved 30 March 2025. "In 1977 and 1978 Hofmann reported that ergonovine maleate was entheogenic,1 a surprising finding in view of its widespread use in obstetrics (Wasson, Hofmann & Ruck 1978; Hofmann 1977). This report was based on a self-experiment conducted by Hofmann on 1 April 1976, with 2.0 mg of ergonovine maleate taken orally. Hofmann reported that this dose manifested a "slightly hallucinogenic activity" lasting more than five hours.2 [...] Our experiments corroborate Hofmann's report that ergonovine possesses entheogenic properties. We found the active dose to lie between 5.0 and 10.0 mg, peroral. It is interesting to note that Hofmann experienced distinct entheogenic effects at 2.0 mg, while Wasson and Ruck did not. Similarly, J.B. experienced distinct entheogenic effects at 3.0 mg, whereas J.O. and P.N. did not. This underscores the importance of metabolic individuality in the uptake and metabolism of mind-altering drugs. With respect to entheogenic effects 10 mg of ergonovine maleate is roughly equivalent to 50 μg is, ergonovine possesses about that LSD-tartrate, 1/200th the entheogenic potency of LSD.". 
  8. ↑ "Images in cardiology: A coronary organic stenosis distal to severe, ergonovine induced spasm: decision making". Heart 91 (10): 1310. October 2005. doi:10.1136/hrt.2004.058560. PMID 16162623. 
  9. ↑ "Differences between coronary hyperresponsiveness to ergonovine and vasospastic angina". Japanese Heart Journal 41 (3): 257–268. May 2000. doi:10.1536/jhj.41.257. PMID 10987346. 
  10. ↑ "Ergometrine drug information". DrugsUpdate.com. http://www.drugsupdate.com/generic/view/138. 
  11. ↑ "Prophylactic ergometrine-oxytocin versus oxytocin for the third stage of labour". The Cochrane Database of Systematic Reviews 2004 (1). 2004. doi:10.1002/14651858.CD000201.pub2. PMID 14973949. 
  12. ↑ "Differential binding of ergot compounds to human versus rat 5-HT2 cortical receptors". Biol Signals 3 (5): 223–229. 1994. doi:10.1159/000109549. PMID 7704103. 
  13. ↑ 13.0 13.1 "Crystal Structure of an LSD-Bound Human Serotonin Receptor". Cell 168 (3): 377–389.e12. January 2017. doi:10.1016/j.cell.2016.12.033. PMID 28129538. 
  14. ↑ "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. 2014. doi:10.1016/j.vascn.2013.12.004. PMID 24361689. 
  15. ↑ 15.0 15.1 "Argyreia nervosa (Burm. f.): receptor profiling of lysergic acid amide and other potential psychedelic LSD-like compounds by computational and binding assay approaches". J Ethnopharmacol 148 (2): 492–497. July 2013. doi:10.1016/j.jep.2013.04.044. PMID 23665164. 
  16. ↑ Drug Discovery: a History (Rev. and updated ed.). Chichester: Wiley. 2005. p. 349. ISBN 978-0-471-89979-2. https://books.google.com/books?id=Cb6BOkj9fK4C&pg=PA349. 
  17. ↑ Robert Forte, ed (2008). "[Chapter Two: A Challenging Question and My Answer"]. The Road to Eleusis: Unveiling the Secret of the Mysteries (Thirtieth Anniversary ed.). Berkeley, California: North Atlantic Books. pp. 35–44. ISBN 978-1-55643-752-6. https://the-eye.eu/tasra/pages/DavidsWelt/media/16305.pdf#page=37. 
  18. ↑ Albert Hofmann (1968). "Psychotomimetic Agents". Drugs Affecting the Central Nervous System. 2. New York: M. Dekker. pp. 169–235. OCLC 245452885. https://archive.org/details/drugsaffectingce0000edit/page/169/mode/1up. "Psychotomimetic effects are unknown for ergometrine, which is used to a large extent in obstetrics as a uterotonic and hemostatic agent. In small dosages, which are administered for this purpose, the alkaloid apparently has no action on the psychic functions. Its occurrence in the alkaloid mixture of ololiuqui can thus have no significant effects on its mental action." 
  19. ↑ "Indolealkylamines and Related Compounds". Hallucinogenic Agents. Bristol: Wright-Scientechnica. 1975. pp. 98–144. ISBN 978-0-85608-011-1. OCLC 2176880. https://bitnest.netfirms.com/external/Books/978-0-85608-011-1. "d-Lysergic acid amide (ergine) is the major constituent of the seeds of both Rivea corymbosa and Ipomoea violacea, together with smaller amounts of d-isolysergic acid amide (isoergine), chanoclavine, elymoclavine, and the N-(1-hydroxyethyl)amides of lysergic and isolysergic acids. [...] Lysergol is found in Rivea but not in Ipomoea, while ergometrine (ergonovine) is present in the latter but not the former (Hofmann and Tscherter, 1960; Hofmann, 1961b, 1964; Hofmann and Cerletti, 1961; Greger, 1963). [...] [...] It is clear that the pharmacologically active constituents of ololiuqui are the isomeric lysergic acid amides. [...] [...] Certainly elymoclavine, lysergol, chanoclavine, and ergometrine produce no psychic changes in man (Isbell and Gorodetzky, 1966; Hofmann, 1968), though the first two do produce central excitation in animals (Yui and Takeo, 1958). [...] Five-hundred seeds of certain ornamental Ipomoea varieties contain as much as 1 mg. of ergometrine, which is usually considered to be an effective oxytocic in doses as low as 0·2-0·5 mg." 
  20. ↑ Risk assessment of Argyreia nervosa (Report). 2020. doi:10.21945/rivm-2019-0210. https://www.rivm.nl/bibliotheek/rapporten/2019-0210.pdf. "Some of the ergot alkaloids assessed by EFSA, ergometrine and ergometrinine, do occur in A. nervosa, however in lesser amounts than the main active alkaloids LSA and iso-LSA. [...] Iso-LSA and LSA were most prominent with relative amounts of 31% and 23% of total alkaloids, respectively. Other ergot alkaloids present included, amongst others, lysergic acid-α-hydroxy ethyl amide (5.8% of total alkaloids) and ergometrine (8.2% of total alkaloids) (Chao & Der Marderosian, 1973)." 
  21. ↑ "Psychotomimetic Agents". Psychopharmacological Agents: Use, Misuse and Abuse. Medicinal Chemistry: A Series of Monographs. 4. Academic Press. 1976. pp. 59–146. doi:10.1016/b978-0-12-290559-9.50011-9. ISBN 978-0-12-290559-9. https://bitnest.netfirms.com/external/10.1016/B978-0-12-290559-9.50011-9. "Ergometrine has, of course, been extensively used in clinical work as an oxytocic following the latter stages of labor at dosages frequently in excess of a milligram, and although nausea can be encountered as an undesirable side reaction, there appears to be no adverse effects of a psychopharmacological nature. [...] It appears that the agents that are responsible for the human activity of these plants are ergine and isoergine, and possibly the corresponding α-hydroxyethylamides of lysergic acid which could serve as metabolic precursors." 
  22. ↑ 22.0 22.1 "St Anthony's fire and living ligatures: a short history of ergometrine". Lancet 359 (9319): 1768–1770. May 2002. doi:10.1016/S0140-6736(02)08658-0. PMID 12049883. 
  23. ↑ "The Substance Responsible for the Traditional Clinical Effect of Ergot". British Medical Journal 1 (3871): 520–523. March 1935. doi:10.1136/bmj.1.3871.520. PMID 20778930. 
  24. ↑ "Targeting the 5-HT system: Potential side effects". Neuropharmacology 179. November 2020. doi:10.1016/j.neuropharm.2020.108233. PMID 32805212. 
  25. ↑ "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. 1993. p. 146. ISBN 978-1-4384-1741-7. 
  26. ↑ "Interview with an Alchemist: Bear Owsley Interview". Bruce Eisner's Writings. January 10, 2004. http://www.bruceeisner.com/writings/2004/01/interview_with__2.html. 
  27. ↑ Connie Littlefield (2002). Hofmann's Potion. Conceptafilm.
  28. ↑ "The Genus Periglandula and Its Symbiotum with Morning Glory Plants (Convolvulaceae)" (in en). Physiology and Genetics. Cham: Springer International Publishing. February 3, 2018. pp. 131–147. doi:10.1007/978-3-319-71740-1_5. ISBN 978-3-319-71739-5. http://link.springer.com/10.1007/978-3-319-71740-1_5. Retrieved 2024-11-21. 
  29. ↑ "Identification and determination of ergot alkaloids in Morning Glory cultivars". Analytical and Bioanalytical Chemistry 408 (12): 3093–3102. May 2016. February 14, 2016. doi:10.1007/s00216-016-9322-5. PMID 26873205. 
  30. ↑ "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. 1993. p. 146. ISBN 978-1-4384-1741-7. 
  31. ↑ Hofmann A (1963). "The Active Principles of the Seeds of Rivea corymbosa and Ipomoea violacea". Harvard Botanical Museum Leaflets (Harvard University Herbaria) 20 (6): 194-212 (19 pgs.). doi:10.5962/p.168542. https://archive.org/details/biostor-160836. 
  32. ↑ "List of Precursors and Chemicals Frequently Used in the Illicit Manufacture of Narcotic Drugs and Psychotropic Substances Under International Control". Vienna, Austria: International Narcotics Control Board. January 2007. http://www.incb.org/pdf/e/list/red.pdf. 

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