Chemistry:Methylergometrine
 | |
| Clinical data | |
|---|---|
| Trade names | Methergine |
| Other names | Methylergonovine; methylergobasin; Methylergobasine; Methylergobrevin; d-Lysergic acid 1-butanolamide; N-[(2S)-1-Hydroxybutan-2-yl]-6-methyl-9,10-didehydroergoline-8β-carboxamide |
| AHFS/Drugs.com | International Drug Names |
| MedlinePlus | a601077 |
| Pregnancy category |
|
| Routes of administration | Oral |
| ATC code | |
| Legal status | |
| Legal status |
|
| Pharmacokinetic data | |
| Metabolism | Liver |
| Elimination half-life | 30–120 minutes |
| Excretion | Mostly bile |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| IUPHAR/BPS | |
| ChemSpider | |
| UNII | |
| ChEMBL | |
| Chemical and physical data | |
| Formula | C20H25N3O2 |
| Molar mass | 339.439 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 172 °C (342 °F) |
| Solubility in water | Insoluble mg/mL (20 °C) |
| |
| |
  (what is this?) (verify) | |
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 in the treatment of migraine. It reportedly produces psychedelic effects similar to those of lysergic acid diethylamide (LSD) at high doses.[citation needed]
It is on the World Health Organization's List of Essential Medicines.[1]
Medical uses
Obstetric use
Methylergometrine is a smooth muscle constrictor that mostly acts on the uterus. It is most commonly used to prevent or control excessive bleeding following childbirth and spontaneous or elective abortion, and also to aid in expulsion of retained products of conception after a missed abortion (miscarriage in which all or part of the fetus remains in the uterus) and to help deliver the placenta after childbirth. It is available as tablets or injection (IM or IV) or in liquid form to be taken orally.[2][3][4]
Migraine
Methylergometrine is sometimes used for both prevention[5] and acute treatment[6] of migraine. It is an active metabolite of methysergide.[7] In the treatment of cluster headaches, methylergometrine has been initiated at a dose of 0.2 mg/day, rapidly increased to 0.2 mg three times per day, and increased to a maximum of 0.4 mg three times per day.[7]
Contraindications
Methylergometrine is contraindicated in patients with hypertension and pre-eclampsia.[2] It is also contraindicated in HIV positive patients taking protease inhibitors, delavirdine, and efavirenz (which is also an agonist at the 5-HT2A–mGlu2 receptor protomer and increases the chances of a patient experiencing hallucinations during methylergometrine therapy).[8]
Side effects
Adverse effects include:[2]
- Nausea, vomiting, and diarrhea
- Dizziness
- Pulmonary hypertension[citation needed]
- Coronary artery vasoconstriction
- Severe systemic hypertension (especially in patients with pre-eclampsia)
- Convulsions
In excessive doses, methylergometrine can also lead to cramping, respiratory depression and coma.[2]
Interactions
Methylergometrine likely interacts with drugs that inhibit the liver enzyme CYP3A4, such as azole antifungals, macrolide antibiotics and many HIV drugs. It can also increase constriction of blood vessels caused by sympathomimetic drugs and other ergot alkaloids.[2]
Pharmacology
Pharmacodynamics
Methylergometrine is an agonist or antagonist to serotonin, dopamine, and α-adrenergic receptors. Its specific binding and activation pattern on these receptors leads to a highly, if not completely, specific contraction of smooth uterus muscle via serotonin 5-HT2A receptors,[9] while blood vessels are affected to a lesser extent compared to other ergot alkaloids.[2] It has been found to interact with the serotonin 5-HT1A, 5-HT1B, 5-HT1E, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5A, and 5-HT7 receptors.[10][11][12][13]
Methylergometrine is a synthetic analogue of ergometrine, a psychedelic alkaloid found in ergot, and many species of morning glory. Methylergometrine is a member of the ergoline family and chemically similar to LSD, ergine, ergometrine, and lysergic acid. According to Jonathan Ott, methylergometrine produces LSD-like psychedelic effects at doses of 2 mg and above.[14] This can be attributed to due to its agonistic action at the 5-HT2A–mGlu2 receptor protomers.[citation needed] Clinical efficacy occurs around 200 µg, ten times lower than the hallucinogenic threshold.[14]
Methylergometrine is an agonist of the serotonin 5-HT2B receptor and is maybe linked to cardiac valvulopathy.[15]
| Site | Affinity (Ki [nM]) | Efficacy (Emax [%]) | Action |
|---|---|---|---|
| 5-HT1A | 1.5–2.0 | ? | Full agonist |
| 5-HT1B | 251 | ? | Full agonist |
| 5-HT1D | 0.86–2.9 | 70 | Partial agonist |
| 5-HT1E | 89 | ? | Full agonist |
| 5-HT1F | 31 | ? | Full agonist |
| 5-HT2A | 0.35–1.1 | ? | Full agonist |
| 5-HT2B | 0.46–2.2 | ? | Full or partial agonist |
| 5-HT2C | 4.6–43.7 | ? | Full agonist |
| 5-HT3 | ? | – | – |
| 5-HT5A | ? | 24.4[13] | Full agonist[13] |
| 5-HT6 | ? | ? | Full agonist |
| 5-HT7 | 11–52 | ? | Full agonist |
| Notes: All sites are human except 5-HT1B (rat) and 5-HT7 (guinea pig).[10][11] | |||
Chemistry
Methylergometrine, also known as d-lysergic acid 1-butanolamide, is a derivative of the ergoline and lysergamide classes and is structurally related to ergometrine (d-lysergic acid β-propanolamide) and lysergic acid diethylamide.
References
- ↑ World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. 2021. WHO/MHP/HPS/EML/2021.02.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 (in German) Austria-Codex (62nd ed.). Vienna: Österreichischer Apothekerverlag. 2007. pp. 5193–5. ISBN 978-3-85200-181-4.
- ↑ (in German) Arzneimittelwirkungen (8th ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. 2001. p. 447. ISBN 3-8047-1763-2.
- ↑ "Methergin" (in German). Fachinformation des Arzneimittel-Kompendium der Schweiz. http://www.kompendium.ch/Monographie.aspx?Id=c2bb9f2c-77a5-46c6-b9e5-dfd5b50e7c89&lang=de&MonType=fi.
- ↑ "History of methysergide in migraine". Cephalalgia 28 (11): 1126–1135. November 2008. doi:10.1111/j.1468-2982.2008.01648.x. PMID 18644039.
- ↑ "Efficacy and tolerability of intravenous methylergonovine in migraine female patients attending the emergency department: a pilot open-label study". Head & Face Medicine 5 (21): 21. November 2009. doi:10.1186/1746-160X-5-21. PMID 19895705.
- ↑ 7.0 7.1 "Serotonergic agents in the management of cluster headache". Current Pain and Headache Reports 15 (2): 108–117. April 2011. doi:10.1007/s11916-011-0176-4. PMID 21271306.
- ↑ "Methylergonovine Maleate Monograph for Professionals - Drugs.com". https://www.drugs.com/monograph/methylergonovine-maleate.html.
- ↑ "Ergot Alkaloids and their Derivatives as Ligands for Serotoninergic, Dopaminergic, and Adrenergic Receptors". Ergot: the genus Claviceps. CRC Press. 1999. pp. 411–440. ISBN 978-905702375-0.
- ↑ 10.0 10.1 Cite error: Invalid
<ref>tag; no text was provided for refs namedPDSPKiDatabase - ↑ 11.0 11.1 Cite error: Invalid
<ref>tag; no text was provided for refs namedPDSPKiDatabase2 - ↑ Cite error: Invalid
<ref>tag; no text was provided for refs namedOlivierWijngaarden1997 - ↑ 13.0 13.1 13.2 "Inactive and active state structures template selective tools for the human 5-HT5A receptor". Nature Structural & Molecular Biology 29 (7): 677–687. July 2022. doi:10.1038/s41594-022-00796-6. PMID 35835867.
- ↑ 14.0 14.1 "Entheogenic (hallucinogenic) effects of methylergonovine". Journal of Psychedelic Drugs 12 (2): 165–166. 1980. doi:10.1080/02791072.1980.10471568. PMID 7420432.
- ↑ "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.
 |  |
