Methylergometrine

{{Short description|Chemical compound}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 403104775 | image = Methylergometrin.svg | image_class = skin-invert-image | width = 200px | image2 = Methylergometrine 3D.png | image_class2 = bg-transparent | width2 = 200px

| tradename = Methergine | Drugs.com = {{drugs.com|international|methylergometrine}} | MedlinePlus = a601077 | pregnancy_AU = | pregnancy_US = | pregnancy_category = Contraindicated | routes_of_administration = Oral | class = Monoamine receptor modulator; Oxytocic; Antimigraine agent; Serotonergic psychedelic; Hallucinogen | ATC_prefix = G02 | ATC_suffix = AB01

| bioavailability = Oral: 60%<ref name="DrugBank" /> {{Abbrlink|IM|Intramuscular injection}}: 78%<ref name="DrugBank" /> | protein_bound = | metabolism = Liver (extensive first-pass metabolism)<ref name="DrugBank" /> | onset = | elimination_half-life = 3.4 hours<ref name="DrugBank">{{cite web | title = Methylergometrine: Uses, Interactions, Mechanism of Action | date = 19 November 1946 | website = DrugBank Online | url = https://go.drugbank.com/drugs/DB00353 | access-date = 10 October 2025 }}</ref> | duration_of_action = | excretion = Mostly bile

| IUPHAR_ligand = 150 | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 113-42-8 | DrugBank = DB00353 | PubChem = 8226 | KEGG = D08207 | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | ChemSpiderID = 7933 | UNII_Ref = {{fdacite|changed|FDA}} | UNII = W53L6FE61V | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 1201356 | synonyms = Methylergonovine; methylergobasin; Methylergobasine; Methylergobrevin; ''d''-Lysergic acid 1-butanolamide; ''N''-[(2''S'')-1-Hydroxybutan-2-yl]-6-methyl-9,10-didehydroergoline-8β-carboxamide

| IUPAC_name = (6''aR'',9''R'')-''N''-[(2''S'')-1-hydroxybutan-2-yl]-7-methyl-6,6a,8,9-tetrahydro-4''H''-indolo[4,3-fg]quinoline-9-carboxamide | C=20 | H=25 | N=3 | O=2 | SMILES = CC[C@@H](CO)NC(=O)[C@@H]2/C=C1/c3cccc4N\C=C(\C[C@H]1N(C)C2)c34 | StdInChI_Ref = {{stdinchicite|changed|chemspider}} | StdInChI = 1S/C20H25N3O2/c1-3-14(11-24)22-20(25)13-7-16-15-5-4-6-17-19(15)12(9-21-17)8-18(16)23(2)10-13/h4-7,9,13-14,18,21,24H,3,8,10-11H2,1-2H3,(H,22,25)/t13-,14+,18-/m1/s1 | StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} | StdInChIKey = UNBRKDKAWYKMIV-QWQRMKEZSA-N

| melting_point = 172 | melting_high = | solubility = Insoluble }}

'''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.<ref>{{cite journal | vauthors = Ott J, Neely P | title = Entheogenic (hallucinogenic) effects of methylergonovine | journal = Journal of Psychedelic Drugs | volume = 12 | issue = 2 | pages = 165–166 | date = April 1980 | pmid = 7420432 | doi = 10.1080/02791072.1980.10471568 }}</ref>

==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.<ref name="Austria-Codex">{{cite book | veditors = Jasek W | title = Austria-Codex | location = Vienna | pages = 5193–5195 | year = 2007 | publisher = Österreichischer Apothekerverlag | edition = 62nd | isbn = 978-3-85200-181-4 | language = German }}</ref><ref>{{cite book | vauthors = Mutschler E, Schäfer-Korting M | title = Arzneimittelwirkungen | location = Stuttgart | page = 447 | year = 2001 | language = German | publisher = Wissenschaftliche Verlagsgesellschaft | edition = 8th | isbn = 978-3-8047-1763-3 }}</ref><ref>{{cite book | chapter = Methergin | title = Fachinformation des Arzneimittel-Kompendium der Schweiz | chapter-url = http://www.kompendium.ch/Monographie.aspx?Id=c2bb9f2c-77a5-46c6-b9e5-dfd5b50e7c89&lang=de&MonType=fi | language = German }}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>

===Migraine=== Methylergometrine is sometimes used for both prevention<ref>{{cite journal | vauthors = Koehler PJ, Tfelt-Hansen PC | title = History of methysergide in migraine | journal = Cephalalgia | volume = 28 | issue = 11 | pages = 1126–1135 | date = November 2008 | pmid = 18644039 | doi = 10.1111/j.1468-2982.2008.01648.x | s2cid = 22433355 }}</ref> and acute treatment<ref>{{cite journal | vauthors = Niño-Maldonado AI, Caballero-García G, Mercado-Bochero W, Rico-Villademoros F, Calandre EP | title = Efficacy and tolerability of intravenous methylergonovine in migraine female patients attending the emergency department: a pilot open-label study | journal = Head & Face Medicine | volume = 5 | issue = 21 | date = November 2009 | pmid = 19895705 | pmc = 2780385 | doi = 10.1186/1746-160X-5-21 | doi-access = free | article-number = 21 }}</ref> of migraine. It is an active metabolite of methysergide.<ref name="Lambru_2011">{{cite journal | vauthors = Lambru G, Matharu M | title = Serotonergic agents in the management of cluster headache | journal = Current Pain and Headache Reports | volume = 15 | issue = 2 | pages = 108–117 | date = April 2011 | pmid = 21271306 | doi = 10.1007/s11916-011-0176-4 | s2cid = 34063682 }}</ref> 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.<ref name="Lambru_2011" />

==Contraindications== Methylergometrine is contraindicated in patients with hypertension and pre-eclampsia.<ref name="Austria-Codex" /> 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).<ref>{{cite web | title = Methylergonovine Maleate Monograph for Professionals | url = https://www.drugs.com/monograph/methylergonovine-maleate.html | work = Drugs.com | url-status = live | archive-url = https://web.archive.org/web/20160920031804/https://www.drugs.com/monograph/methylergonovine-maleate.html | archive-date = 2016-09-20 }}</ref>

==Side effects== Adverse effects include:<ref name="Austria-Codex" />

* Nausea, vomiting, and diarrhea * Dizziness * Pulmonary hypertension{{citation needed|date=July 2012}} * 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.<ref name="Austria-Codex" />

== Interactions ==

{{See also|Psychedelic drug#Interactions|Trip killer#Serotonergic psychedelic antidotes}}

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.<ref name="Austria-Codex" />

==Pharmacology== ===Pharmacodynamics=== {| class="wikitable floatleft" style="font-size:small;" |+ {{Nowrap|Methylergometrine activities}} ! 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 | ? | Agonist |- | 5-HT2C | 4.6–43.7 | ? | Full agonist |- | 5-HT3 | ? | – | – |- | 5-HT5A | ? | 24.4<ref name="Zhang_2022" /> | Full agonist<ref name="Zhang_2022" /> |- | 5-HT6 | ? | ? | Full agonist |- | 5-HT7 | 11–52 | ? | Full agonist |- class="sortbottom" | colspan="4" style="width: 1px; background-color:var(--background-color-notice-subtle,#eaecf0); color:inherit; text-align: center;" | '''Notes:''' All sites are human except 5-HT1B (rat) and 5-HT7 (guinea pig). '''Refs:''' <ref name="PDSPKiDatabase">{{cite web | title = PDSP Database - UNC | url = https://pdsp.unc.edu/databases/pdsp.php?testFreeRadio=testFreeRadio&testLigand=Methylergonovine&doQuery=Submit+Query | website = pdsp.unc.edu | access-date = 15 January 2022 | archive-url = https://web.archive.org/web/20210416001542/https://pdsp.unc.edu/databases/pdsp.php?testFreeRadio=testFreeRadio&testLigand=Methylergonovine&doQuery=Submit+Query | archive-date = 16 April 2021 }}</ref><ref name="PDSPKiDatabase2">{{cite web | title = PDSP Database - UNC | url = https://pdsp.unc.edu/databases/pdsp.php?testFreeRadio=testFreeRadio&testLigand=Methergine&doQuery=Submit+Query | website = pdsp.unc.edu | access-date = 15 January 2022 | archive-url = https://web.archive.org/web/20210416011555/https://pdsp.unc.edu/databases/pdsp.php?testFreeRadio=testFreeRadio&testLigand=Methergine&doQuery=Submit+Query | archive-date = 16 April 2021 }}</ref><ref name="BindingDB">{{cite web | vauthors = Liu T | title = BindingDB BDBM50330860 CHEMBL1201356::METHYLERGONOVINE::Methylergometrine | website = BindingDB | url = https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50330860 | access-date = 1 November 2024 }}</ref> ''Additional refs:'' <ref name="Rothman_2000">{{cite journal | vauthors = Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, Roth BL | title = Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications | journal = Circulation | volume = 102 | issue = 23 | pages = 2836–2841 | date = December 2000 | pmid = 11104741 | doi = 10.1161/01.cir.102.23.2836 | doi-access = free | author7-link = Bryan Roth }}</ref><ref name="Guzman_2020">{{cite journal | vauthors = Guzman M, Armer T, Borland S, Fishman R, Leyden M | title = Novel Receptor Activity Mapping of Methysergide and its Metabolite, Methylergometrine, Provides a Mechanistic Rationale for both the Clinically Observed Efficacy and Risk of Fibrosis in Patients with Migraine | journal = Neurology | volume = 94 | issue = 15 Supplement | date = April 2020 | doi = 10.1212/WNL.94.15_supplement.2663 | id = 2663 | s2cid = 266103427 | url = https://www.xocpharma.com/file.cfm/7/docs/AHS_2019_Poster_1_XocPharma_Final.pdf | archive-date = 2023-05-29 | access-date = 2021-04-16 | archive-url = https://web.archive.org/web/20230529232959/https://www.xocpharma.com/file.cfm/7/docs/AHS_2019_Poster_1_XocPharma_Final.pdf }}</ref><ref name="Olivier_1997">{{cite book | vauthors = Olivier B, van Wijngaarden I, Soudijn W | title = Serotonin Receptors and their Ligands | pages = 149– | date = 10 July 1997 | url = https://books.google.com/books?id=lfo0hGqIex0C&pg=PA149 | publisher = Elsevier | isbn = 978-0-08-054111-2 }}</ref><ref name="Leff_1998">{{cite book | vauthors = Leff P | title = Receptor - Based Drug Design | pages = 181–182 | date = 10 April 1998 | url = https://books.google.com/books?id=YYk04RMvSSUC&pg=PA181 | publisher = CRC Press | isbn = 978-1-4200-0113-6 }}</ref><ref name="Pertz_1999">{{cite book | vauthors = Pertz H, Eich E | chapter = Ergot Alkaloids and their Derivatives as Ligands for Serotoninergic, Dopaminergic, and Adrenergic Receptors | title = Ergot | pages = 432–462 | year = 1999 | doi = 10.1201/9780203304198-21 | isbn = 978-0-429-21976-4 | chapter-url = http://chemistry.mdma.ch/hiveboard/palladium/pdf/Ergot%20-%20The%20Genus%20Claviceps%20%281999%29/TF3168ch14.pdf | archive-url = https://web.archive.org/web/20210416003930/http://chemistry.mdma.ch/hiveboard/palladium/pdf/Ergot%20-%20The%20Genus%20Claviceps%20%281999%29/TF3168ch14.pdf | archive-date = 2021-04-16 }}</ref> |}

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,<ref>{{cite book | vauthors = Pertz H, Eich E | veditors = Křen V, Cvak L | chapter = Ergot Alkaloids and their Derivatives as Ligands for Serotonergic, Dopaminergic, and Adrenergic Receptors | title = Ergot: the genus Claviceps | pages = 411–440 | year = 1999 | publisher = CRC Press }}</ref> while blood vessels are affected to a lesser extent compared to other ergot alkaloids.<ref name="Austria-Codex" /> 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.<ref name="PDSPKiDatabase" /><ref name="PDSPKiDatabase2" /><ref name="Olivier_1997" /><ref name="Zhang_2022">{{cite journal | vauthors = Zhang S, Chen H, Zhang C, Yang Y, Popov P, Liu J, Krumm BE, Cao C, Kim K, Xiong Y, Katritch V, Shoichet BK, Jin J, Fay JF, Roth BL | title = Inactive and active state structures template selective tools for the human 5-HT5A receptor | journal = Nature Structural & Molecular Biology | volume = 29 | issue = 7 | pages = 677–687 | date = July 2022 | pmid = 35835867 | pmc = 9299520 | doi = 10.1038/s41594-022-00796-6 }}</ref> Methylergometrine is an agonist of the serotonin 5-HT2B receptor and may be linked to cardiac valvulopathy.<ref name="Cavero_2014">{{cite journal | vauthors = Cavero I, Guillon JM | title = Safety Pharmacology assessment of drugs with biased 5-HT(2B) receptor agonism mediating cardiac valvulopathy | journal = Journal of Pharmacological and Toxicological Methods | volume = 69 | issue = 2 | pages = 150–161 | date = 2014 | pmid = 24361689 | doi = 10.1016/j.vascn.2013.12.004 }}</ref>

===Pharmacokinetics=== The bioavailability of methylergometrine is 60% via oral administration and 78% by intramuscular injection.<ref name="DrugBank" /> It is metabolized in the liver, with extensive first-pass metabolism.<ref name="DrugBank" /> The elimination half-life of the drug is 3.4{{nbsp}}hours.<ref name="DrugBank" /> It is eliminated mainly via metabolism and then excreted.<ref name="DrugBank" />

==Natural occurrence== Previously thought to be an exclusively synthetic compound, it has been reported to occur naturally in ''Argyreia nervosa'' (Hawaiian baby woodrose).<ref name="Chen_2020">{{cite report | vauthors = Chen W, De Wit-Bos L | title = Risk assessment of Argyreia nervosa | date = 2020 | doi = 10.21945/rivm-2019-0210 | url = https://www.rivm.nl/bibliotheek/rapporten/2019-0210.pdf }}</ref><ref name="Paulke_2015">{{cite journal | vauthors = Paulke A, Kremer C, Wunder C, Wurglics M, Schubert-Zsilavecz M, Toennes SW | title = Studies on the alkaloid composition of the Hawaiian Baby Woodrose Argyreia nervosa, a common legal high | journal = Forensic Science International | volume = 249 | pages = 281–293 | date = April 2015 | pmid = 25747328 | doi = 10.1016/j.forsciint.2015.02.011 }}</ref> The drug is on the World Health Organization's List of Essential Medicines.<ref name="World_Health_Organization_2021">{{cite book | title = World Health Organization model list of essential medicines: 22nd list (2021) | location = Geneva | year = 2021 | hdl = 10665/345533 | publisher = World Health Organization | id = WHO/MHP/HPS/EML/2021.02 | hdl-access = free }}</ref>

==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 (LSD).

==History== Methylergometrine was first described in the scientific literature by 1945.<ref name="Hepp_1945">{{cite journal | vauthors = Hepp LC, Evans JR | title = Clinical comparison of methergine and natural ergonovine | journal = Rocky Mountain Medical Journal | volume = 42 | page = 949 | date = December 1945 | pmid = 21007486 }}</ref><ref name="Tritsch_1945">{{cite journal | vauthors = Tritsch JE, Schneider E | title = Clinical experience with a new synthetic ergonovine-like substance | journal = American Journal of Obstetrics and Gynecology | volume = 50 | issue = 4 | pages = 434–438 | date = 1945 | doi = 10.1016/0002-9378(45)90148-7 | url = https://linkinghub.elsevier.com/retrieve/pii/0002937845901487 | access-date = 10 October 2025 | url-access = subscription }}</ref>

==Society and culture== ===Recreational use=== 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.<ref name="Ott_1980">{{cite journal | vauthors = Ott J, Neely P | title = Entheogenic (hallucinogenic) effects of methylergonovine | journal = Journal of Psychedelic Drugs | volume = 12 | issue = 2 | pages = 165–166 | date = 1980 | pmid = 7420432 | doi = 10.1080/02791072.1980.10471568 }}</ref> Clinical effectiveness of methylergometrine as a medication occurs around 200{{nbsp}}μg, which is 10{{nbsp}}times lower than the hallucinogenic threshold.<ref name="Ott_1980" />

===Legal status=== ====Canada==== Methylergometrine is not controlled substance in Canada.<ref name="CDSA2025">{{cite web | title=Controlled Drugs and Substances Act | website=Department of Justice Canada | date=5 December 2025 | url=https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html | access-date=20 January 2026}}</ref>

====United States==== Methylergometrine is not an explicitly controlled substance in the United States.<ref name="OrangeBook2026">{{citation | title = Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026) | date = January 2026 | publisher = U.S. Department of Justice: Drug Enforcement Administration (DEA): Diversion Control Division | location = United States | url = https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf}}</ref>

==See also== * Substituted lysergamide

==References== {{Reflist}}

==External links== * [https://isomerdesign.com/pihkal/explore/5316 Methylergometrine - Isomer Design] * [https://www.erowid.org/library/books_online/tihkal/tihkal26.shtml LSD-25 (Discusses Methergine) - TiHKAL - Erowid] * [https://isomerdesign.com/pihkal/read/tk/26 LSD-25 (Discusses Methergine) - TiHKAL - Isomer Design] * [https://nervewing.blogspot.com/2020/06/obscure-and-unknown-ergometrine-and.html Hallucinogens You Probably Haven't Heard of: Ergometrine and Methylergometrine - Nervewing - Blogger]

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