Ergonovine

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Ergonovine
Ergonovine-skeletal.svg
Clinical data
Trade names Ergotrate, 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.com Monograph
Pregnancy
category
  • X
Routes of
administration
oral, injection
ATC code
Legal status
Legal status
Pharmacokinetic data
Metabolism Liver (partly CYP3A4)
Elimination half-life 2-phase (10 min; 2 hrs)
Excretion Biliary
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 InfoCard 100.000.441 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C19H23N3O2
Molar mass 325.412 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 Yes check.svgY
  • Key:WVVSZNPYNCNODU-XTQGRXLLSA-N Yes check.svgY
   (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]

Contents

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 [6] It was originally made from the rye ergot fungus but can also be made from lysergic acid.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 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 ] 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 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. [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.

Related Research Articles

<span class="mw-page-title-main">LSD</span> Hallucinogenic drug

Lysergic acid diethylamide, commonly known as LSD, is a potent psychedelic drug that intensifies thoughts, emotions, and sensory perception. Often referred to as acid or lucy, LSD can cause mystical, spiritual, or religious experiences. At higher doses, it primarily induces visual and auditory hallucinations. LSD is not considered addictive, because it does not produce compulsive drug-seeking behavior. Using LSD can lead to adverse psychological reactions, such as anxiety, paranoia, and delusions. Additionally, it may trigger "flashbacks," also known as hallucinogen persisting perception disorder (HPPD), where individuals experience persistent visual distortions after use.

<i>Ipomoea corymbosa</i> Species of plant

Ipomoea corymbosa is a species of morning glory, native throughout Latin America from Mexico as far south as Peru and widely naturalised elsewhere. Its common names include Christmasvine, Christmaspops, and snakeplant.

<span class="mw-page-title-main">Ergine</span> Chemical compound

Ergine, also known as lysergic acid amide and lysergamide, is an ergoline alkaloid that occurs in Clavicipitaceous fungi, which includes Convolvulaceae vines, which have a permanent bond with these fungi. The most common source of ergine for consumers is the seeds of Ipomoea tricolor, Ipomoea corymbosa, and Argyreia nervosa; isoergine and lysergic acid propanolamide have also been shown to contribute to their psychoactivity.

<span class="mw-page-title-main">Ergoline</span> Chemical compound

Ergoline is a core structure in many alkaloids and their synthetic derivatives. Ergoline alkaloids were first characterized in ergot. Some of these are implicated in the condition of ergotism, which can take a convulsive form or a gangrenous form. Even so, many ergoline alkaloids have been found to be clinically useful. Annual world production of ergot alkaloids has been estimated at 5,000–8,000 kg of all ergopeptines and 10,000–15,000 kg of lysergic acid, used primarily in the manufacture of semi-synthetic derivatives.

<span class="mw-page-title-main">Lysergic acid</span> Precursor for a range of ergoline alkaloids produced by the ergot fungus

Lysergic acid, also known as D-lysergic acid and (+)-lysergic acid, is a precursor for a wide range of ergoline alkaloids that are produced by the ergot fungus and found in the seeds of Argyreia nervosa, and Ipomoea species.

<span class="mw-page-title-main">Ergotamine</span> Chemical compound in the ergot family of alkaloids

Ergotamine, sold under the brand name Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It is structurally similar to several neurotransmitters, and it acts as a vasoconstrictor. It is used for acute migraines, sometimes with caffeine as the combination ergotamine/caffeine.

<i>Argyreia nervosa</i> Species of plant

Argyreia nervosa is a perennial climbing vine native to the Indian subcontinent and introduced to numerous areas worldwide, including Hawaii, Africa, and the Caribbean. Though it can be invasive, it is often prized for its aesthetic and medicinal value. Common names include Hawaiian baby woodrose, adhoguda अधोगुडा or vidhara विधारा (Sanskrit), elephant creeper and woolly morning glory. Its seeds are known for their powerful entheogenic properties, greater or similar to those of Ipomoea species, with users reporting significant psychedelic and spiritual experiences. The two botanical varieties are Argyreia nervosa var. nervosa described here, and Argyreia nervosa var. speciosa, the roots of which are used in Ayurvedic medicine.

<span class="mw-page-title-main">Psilocin</span> Chemical compound

Psilocin, also known as 4-hydroxy-N,N-dimethyltryptamine (4-OH-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic. It is present in most psychedelic mushrooms together with its phosphorylated counterpart psilocybin. Psilocin is a Schedule I drug under the Convention on Psychotropic Substances. Acting on the serotonin 5-HT2A receptors, psilocin's psychedelic effects are directly correlated with the drug's occupancy at these receptor sites. The subjective mind-altering effects of psilocin are highly variable and are said to resemble those of lysergic acid diethylamide (LSD) and N,N-dimethyltryptamine (DMT).

<span class="mw-page-title-main">Lysergamides</span> Class of chemical compounds

Amides of lysergic acid are collectively known as lysergamides or ergoamides, and include a number of compounds with potent agonist and/or antagonist activity at various serotonin and dopamine receptors. Lysergamides contain an embedded tryptamine structure, and as a result can produce similar, often psychedelic, effects to those of the true tryptamines.

<span class="mw-page-title-main">ALD-52</span> Chemical compound

ALD-52, also known as 1-acetyl-LSD, has chemical structural features similar to lysergic acid diethylamide (LSD), a known psychedelic drug. Similarly, ALD-52 has been reported to produce psychoactive effects, but its pharmacological effects on humans are poorly understood. Given its psychoactive properties, it has been reported to be consumed as a recreational drug, and the purported first confirmed detection of the substance on the illicit market occurred in April 2016.

<span class="mw-page-title-main">Lysergic acid hydroxyethylamide</span> Chemical compound

ᴅ-Lysergic acid α-hydroxyethylamide, also known as ᴅ-lysergic acid methyl carbinolamide, is an ergoamide and an ergoline. It is perhaps the main constituent of the parasitic fungus, Claviceps paspali; and found in trace amounts in Claviceps Purpurea. C. paspali and C. purpurea are ergot-spreading fungi. Periglandula, Clavicipitacepus fungi, are permanently symbiotically connected to an estimated 450 species of Convolvulaceae and thus generate LAH in some of them. The most well-known ones are Ipomoea tricolor, Turbina corymbosa (coaxihuitl), and Argyreia nervosa.

<span class="mw-page-title-main">Methylergometrine</span> Chemical compound

Methylergometrine, also known as methylergonovine and sold under the brand name Methergine, is a medication of the ergoline and lysergamide groups which is used as an oxytocic in obstetrics and as an antimigraine agent in the treatment of migraine headaches. It reportedly produces psychedelic effects similar to those of lysergic acid diethylamide (LSD) at high doses.

<span class="mw-page-title-main">Lysergol</span> Chemical compound

Lysergol is an alkaloid of the ergoline family that occurs as a minor constituent in some species of fungi, and in the morning glory family of plants (Convolvulaceae), including the hallucinogenic seeds of Rivea corymbosa (ololiuhqui), Argyreia nervosa and Ipomoea violacea. Lysergol is not a controlled substance in the USA. Its possession and sale is also legal under the U.S. Federal Analog Act because it does not have a known pharmacological action or a precursor relationship to LSD, which is a controlled substance. However, lysergol is an intermediate in the manufacture of some ergoloid medicines.

<span class="mw-page-title-main">Indole alkaloid</span> Class of alkaloids

Indole alkaloids are a class of alkaloids containing a structural moiety of indole; many indole alkaloids also include isoprene groups and are thus called terpene indole or secologanin tryptamine alkaloids. Containing more than 4100 known different compounds, it is one of the largest classes of alkaloids. Many of them possess significant physiological activity and some of them are used in medicine. The amino acid tryptophan is the biochemical precursor of indole alkaloids.

<span class="mw-page-title-main">AL-LAD</span> Chemical compound (psychedelic drug)

AL-LAD, also known as 6-allyl-6-nor-LSD, is a psychedelic drug and an analog of lysergic acid diethylamide (LSD). It is described by Alexander Shulgin in the book TiHKAL. It is synthesized starting from nor-LSD as a precursor, using allyl bromide as a reactant.

<span class="mw-page-title-main">LSM-775</span> Chemical compound

N-Morpholinyllysergamide, also known as lysergic acid morpholide, is a derivative of ergine (lysergamide). It is less potent than lysergic acid diethylamide (LSD) but is reported to have some LSD-like effects at doses ranging from 75 to 700 micrograms and a shorter duration. LSM-775 may only produce weak or threshold psychedelic effects in humans.

<span class="mw-page-title-main">Methylisopropyllysergamide</span> Chemical compound

Methylisopropyllysergamide is an analogue of LSD that was originally discovered by Albert Hofmann at Sandoz during the original structure-activity research into LSD. It has subsequently been investigated in more detail by the team led by David E. Nichols at Purdue University. Methylisopropyllysergamide is a structural isomer of LSD, with the alkyl groups on the amide nitrogen having been subjected to a methylene shuffle. MIPLA and its ethylisopropyl homologue EIPLA are the only simple N,N-dialkyl lysergamides that approach the potency of LSD itself, being around 1/3-1/2 the potency of LSD, while all other dialkyl analogues tested are only around 1/10 as potent as LSD, although some N-monoalkyl lysergamides such as the sec-butyl and t-butyl derivatives were also found to show an activity profile and potency comparable to LSD, and the mono-isopropyl derivative is only slightly weaker than MIPLA. Apart from its lower potency, the hallucinogenic effects of methylisopropyllysergamide are similar to those of LSD itself, and the main use for this drug has been in studies of the binding site at the 5-HT2A receptor through which LSD exerts most of its pharmacological effects.

A uterotonic, also known as an oxytocic or ecbolic, is a type of medication used to induce contraction or greater tonicity of the uterus. Uterotonics are used both to induce labor and to reduce postpartum hemorrhage.

<span class="mw-page-title-main">2-Bromo-LSD</span> Chemical compound

2-Bromo-LSD, also known as BOL-148 or as bromolysergide, is a derivative of lysergic acid invented by Albert Hofmann, as part of the original research from which the closely related compound LSD was also derived. It is a non-hallucinogenic serotonin 5-HT2A receptor partial agonist, as well as acting at other targets, with psychoplastogenic and antidepressant-like effects in animals.

<span class="mw-page-title-main">1V-LSD</span> Chemical compound

1V-LSD, sometimes nicknamed Valerie, is a psychotropic substance and a research chemical with psychedelic effects. 1V-LSD is an artificial derivative of natural lysergic acid, which occurs in ergot alkaloids, as well as being an analogue of LSD. 1V-LSD has been sold online until an amendment to the German NpSG was enforced in 2022 which controls 1P-LSD and now 1cP-LSD, 1V-LSD and several other lysergamides.

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