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| Trade names | Ergotrate, Ergotrate Maleate[1][2] |
| Other names | Ergometrine;[3][4] Ergobasin;[3] Ergotocine;[3] Ergostetrine;[3] Lysergic acid propanolamide;[4] Lysergic acid hydroxymethylethylamide;[4] ᴅ-Lysergic acid-1,2-propanolamide;[4] ᴅ-Lysergic acid 1-(hydroxymethyl)ethylamide;[4] ᴅ(+)-Lysergic acid-β-hydroxyisopropylamide[4] |
| AHFS/Drugs.com | Monograph |
| Routes of administration | oral,intramuscular,intravenous |
| Drug class | Serotonin receptor agonists;Uterotonic |
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| Metabolism | Liver (partlyCYP3A4) |
| Eliminationhalf-life | 2-phase (10 min; 2 hrs) |
| Excretion | Bile duct |
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| ECHA InfoCard | 100.000.441 |
| Chemical and physical data | |
| Formula | C19H23N3O2 |
| Molar mass | 325.412 g·mol−1 |
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Ergonovine, also known asergometrine andlysergic acid propanolamide, is amedication used to causecontractions of theuterus to treatheavy vaginal bleeding after childbirth.[6][1] It can be used eitherby mouth, byinjection into a muscle, orinjection into a vein.[6]
Commonside effects includehigh blood pressure,vomiting,seizures,headache, andlow blood pressure.[6] Other serious side effects includeergotism.[6]
Ergonovine was discovered in 1932.[7] It is on theWorld Health Organization's List of Essential Medicines.[8] Ergonovine iscontrolled in some countries because it can be used to make thepsychedelic druglysergic acid diethylamide (LSD).[9] It is also known to produce psychedelic effects itself at high doses.[10][11]
Ergonovine has a medical use inobstetrics to facilitate delivery of theplacenta and to preventbleeding afterchildbirth by causingsmooth muscle tissue in theblood vessel walls to narrow, thereby reducing blood flow. It is usually combined withoxytocin (Syntocinon) assyntometrine. It begins working within 15 minutes when takenby mouth and is faster inonset when used byinjection.[6] Itsduration is between 45 and 180 minutes.[6]
It can induce spasm of thecoronary arteries.[12] It is used to diagnosevariant (Prinzmetal's) angina.[13]
Possible side effects includenausea,vomiting, abdominal pain,diarrhea,headache,dizziness,tinnitus,chest pain,palpitation,bradycardia, transient hypertension and other cardiacarrhythmias,dyspnea,rashes, andshock.[14] An overdose produces a characteristic poisoning,ergotism or "St. Anthony's fire": prolongedvasospasm resulting ingangrene 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.
Ergonovine stimulates the uterus and other smooth muscles. It targetsα-adrenergic,dopaminergic, andserotonin receptors (the5-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 humanserotonin5-HT2A receptor with similaraffinity aslysergic acid diethylamide (LSD).[16][17] Ergonovine is an agonist of the serotonin5-HT2B receptor and has been associated withcardiac valvulopathy.[18][17] A computer-predicted binding profile of ergonovine at an array of serotonin,dopamine, and otherreceptors has been published.[19] It was predicted to bind to most of the serotonin receptors with moderately high affinity, albeit lower than LSD.[19]
Ergonovine was originally made from therye ergot fungus but can also be made fromlysergic acid.[7][20]
Asimplifiedanalogue of ergonovine that was also investigated as an oxytocic istochergamine.
According toAlbert Hofmann and other researchers, although ergonovine isnaturally occurring inmorning glory seeds and is known to producepsychedelic effects at higher doses,[11][21] it is present in too small of amounts to contribute to theirpsychoactive orhallucinogenic effects.[22][23][24][25]
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 ofpostpartum haemorrhage.[26]
Ergonovine was first isolated and obtained by the chemistsC Moir, H W Dudley and Gerald Rogers[citation needed] in 1935.[27][28] Caroline De Costa has argued that the adoption of ergonovine forpreventive use and for treating bleeding contributed to the decline in thematernal mortality rate in much of the West during the early 20th century.[26]
Ergonovine inducespsychedelic effects at doses of 2–10 mg, in contrast to its medical use in doses of 0.2–0.4 mg.[10][11][29][30][31] The most common source of ergonovine for drug users isIpomoea tricolor seeds, as they are the only commonly available natural product that hosts an ergoline-generating fungus.[32] The ergonovine content ofI. tricolor seeds varies between one-tenth and one-third ofergine, an ergonovine analog.[33] One person who had the opportunity to try ergonovine to see its psychedelic potential stated that it was mild relative to other psychedelics, but thatergine may synergize with it;[34] indeed the contrast between Hofmann's self-administration ofIpomoea corymbosa extract and synthetic ergine is apparent in his essay on the initial analysis ofI. corymbosa andI. tricolor seeds.[35][10]
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 ofololiuhqui, 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 theUnited Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances, as possible precursor compound for LSD.[36] As anN-alkyl derivative of ergine, ergonovine is also covered by theMisuse of Drugs Act 1971, effectively rendering it illegal in the United Kingdom.[citation needed]
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.
{{cite journal}}: CS1 maint: bot: original URL status unknown (link)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.
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.
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).
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.
