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{{Short description|Chemical compound}} |
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{{Unreferenced|auto=yes|date=December 2009}} |
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{{cs1 config|name-list-style=vanc|display-authors=6}} |
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{{Drugbox | verifiedrevid = 376108326 |
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{{Drugbox |
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| Verifiedfields = changed |
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| IUPAC_name = 9,10-didehydro- N-- D-lysergamide |
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| Watchedfields = changed |
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| image = Methylergonovine_chemical_structure.png |
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| verifiedrevid = 403104775 |
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| width = 150 |
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| IUPAC_name = (6''aR'',9''R'')-''N''--7-methyl-6,6a,8,9-tetrahydro-4''H''-indoloquinoline-9-carboxamide |
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| CASNo_Ref = {{cascite}} |
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| image = Methylergometrin.svg |
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| width = 150px |
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<!--Clinical data--> |
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| tradename = Methergine |
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| Drugs.com = {{drugs.com|international|methylergometrine}} |
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| MedlinePlus = a601077 |
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| pregnancy_AU = |
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| pregnancy_US = |
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| pregnancy_category = Contraindicated |
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| legal_AU = |
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| legal_CA = |
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| legal_UK = |
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| legal_US = |
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| legal_status = Rx-only |
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| routes_of_administration = ] |
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<!--Pharmacokinetic data--> |
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| bioavailability = |
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| protein_bound = |
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| metabolism = Liver |
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| elimination_half-life = 30–120 minutes |
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| excretion = Mostly bile |
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<!--Identifiers--> |
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| IUPHAR_ligand = 150 |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 113-42-8 |
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| CAS_number = 113-42-8 |
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| DrugBank = DB00353 |
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| ATC_prefix = G02 |
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| ATC_prefix = G02 |
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| ATC_suffix = AB01 |
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| ATC_suffix = AB01 |
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| PubChem = 8226 |
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| PubChem = 8226 |
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| KEGG = D08207 |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = 7933 |
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| UNII_Ref = {{fdacite|changed|FDA}} |
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| UNII = W53L6FE61V |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 1201356 |
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| synonyms = Methylergonovine; methylergobasin; Methylergobasine; Methylergobrevin; ''d''-Lysergic acid 1-butanolamide; ''N''--6-methyl-9,10-didehydroergoline-8β-carboxamide |
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<!--Chemical data--> |
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| C=20 | H=25 | N=3 | O=2 |
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| C=20 | H=25 | N=3 | O=2 |
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| SMILES = CC(CO)NC(=O)2/C=C1/c3cccc4N\C=C(\C1N(C)C2)c34 |
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| molecular_weight = 339.432 g/mol |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| synonyms = Methylergobasine<br /> Methylergobrevin<br /> Methylergonovine |
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| 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 |
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| smiles = CC(CO)NC(=O)2/C=C1/c3cccc4N\C=C(\C1N(C)C2)c34 |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| solubility = insoluble |
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| StdInChIKey = UNBRKDKAWYKMIV-QWQRMKEZSA-N |
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<!--Physical data--> |
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| melting_point = 172 |
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| melting_point = 172 |
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| melting_high = |
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| melting_high = |
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| solubility = Insoluble |
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| bioavailability = |
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| protein_bound = |
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| metabolism = liver |
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| elimination_half-life = 30-120 min |
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| excretion = |
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| pregnancy_AU = |
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| pregnancy_US = C |
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| pregnancy_category = |
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| legal_AU = |
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| legal_CA = |
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| legal_UK = |
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| legal_US = |
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| legal_status = Rx-only |
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| routes_of_administration = |
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}} |
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}} |
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'''Methylergometrine''' (other names include '''methylergonovine''', '''methylergobasin''', '''methergine''', and d-] 1-]]) is a ] ] of ], a ] ] found in ], and many species of ]. It is a member of the ] family and chemically similar to ], ], ], and ]. Due to its ] properties, it has a medical use in ]. According to ], methylergonovine has ]-like actions above 2 milligrams{{Citation needed|date=April 2010}}. Clinical dosages are ten times lower. |
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'''Methylergometrine''', also known as '''methylergonovine''' and sold under the brand name '''Methergine''', is a ] of the ] and ] groups which is used as an ] in ] and as an ] in the treatment of ] ]s. It reportedly produces ] effects similar to those of ] (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> |
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'''Methylergometrine maleate''' is marketed under the trade name '''Methergine'''. |
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It is on the ].<ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref> |
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==Obstetric use== |
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Methylergometrine is a blood vessel constrictor and smooth muscle agonist most commonly used to prevent or control excessive bleeding following childbirth and spontaneous or elective abortion. It also causes uterine contractions 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 (] or ]) or in liquid form to be taken orally. |
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==Medical uses== |
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===Obstetric use=== |
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Methylergometrine is a smooth muscle constrictor that mostly acts on the ]. 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 (] or ]) or in liquid form to be taken orally.<ref name="Austria-Codex">{{cite book |title=Austria-Codex| veditors = Jasek W |publisher=Österreichischer Apothekerverlag |location=Vienna |year=2007 |edition=62nd |isbn=978-3-85200-181-4 |pages=5193–5 |language=German }}</ref><ref>{{cite book | vauthors = Mutschler E, Schäfer-Korting M |title= Arzneimittelwirkungen |language=German |location=Stuttgart |publisher=Wissenschaftliche Verlagsgesellschaft |year=2001 |edition=8th |page=447 |isbn=3-8047-1763-2 }}</ref><ref>{{cite book | 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 | chapter = Methergin | language = German }}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> |
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===Migraine=== |
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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 | pages = 21 | date = November 2009 | pmid = 19895705 | pmc = 2780385 | doi = 10.1186/1746-160X-5-21 | doi-access = free }}</ref> of migraine. It is an ] of ].<ref name="pmid21271306">{{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 ]s, 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="pmid21271306" /> |
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==Contraindications== |
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Methylergometrine is contraindicated in patients with ] and ].<ref name="Austria-Codex" /> It is also contraindicated in ] positive patients taking ], ], and ] (which is also an agonist at the 5-HT<sub>2A</sub>–mGlu2 receptor protomer and increases the chances of a patient experiencing hallucinations during methylergometrine therapy).<ref>{{cite web|url=https://www.drugs.com/monograph/methylergonovine-maleate.html|title=Methylergonovine Maleate Monograph for Professionals | 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> |
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==Side effects== |
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==Side effects== |
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Adverse effects include:<ref name="Austria-Codex" /> |
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* ] effects such as nausea, vomiting, and diarrhea |
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* Cramping |
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* Nausea, vomiting, and diarrhea |
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* Dizziness |
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* Dizziness |
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* Pulmonary hypertension |
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* Pulmonary hypertension{{citation needed|date=July 2012}} |
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* Coronary artery vasoconstriction |
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* Coronary artery vasoconstriction |
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* Severe systemic hypertension (especially in patients with preeclampsia) |
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* Severe systemic hypertension (especially in patients with ]) |
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* Convulsions |
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In excessive doses, methylergometrine can also lead to cramping, ] and coma.<ref name="Austria-Codex" /> |
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==Contraindications== |
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* ] |
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* Pregnancy |
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==Interactions== |
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{{Oxytocics}} |
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Methylergometrine likely interacts with drugs that inhibit the liver enzyme ], such as ]s, ]s and many HIV drugs. It can also increase constriction of blood vessels caused by ] drugs and other ergot alkaloids.<ref name="Austria-Codex" /> |
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{{Hallucinogenic lysergamides}} |
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==Pharmacology== |
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===Pharmacodynamics=== |
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Methylergometrine is an ] or ] to ], ], and ]s. Its specific binding and activation pattern on these receptors leads to a highly, if not completely, specific contraction of smooth uterus muscle via serotonin ]s,<ref>{{cite book | vauthors = Pertz H, Eich E | chapter = Ergot Alkaloids and their Derivatives as Ligands for Serotoninergic, Dopaminergic, and Adrenergic Receptors | veditors = Křen V, Cvak L |title=Ergot: the genus Claviceps |year=1999 |publisher=CRC Press |isbn=978-905702375-0 |pages=411–440 }}</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 ], ], ], ], ], ], ], ], and ]s.<ref name="PDSPKiDatabase" /><ref name="PDSPKiDatabase2" /><ref name="OlivierWijngaarden1997" /><ref name=":0">{{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-HT<sub>5A</sub> 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> |
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Methylergometrine is a ] ] of ], a ] ] found in ], and many species of ]. Methylergometrine is a member of the ] family and chemically similar to ], ], ], and ]. According to ], methylergometrine produces LSD-like ] effects at doses of 2 mg and above.<ref name="pmid7420432">{{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> This can be attributed to due to its agonistic action at the 5-HT<sub>2A</sub>–] receptor ]s.{{Citation needed|date=April 2021}} Clinical efficacy occurs around 200 μg, ten times lower than the hallucinogenic threshold.<ref name="pmid7420432" /> |
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{{genito-urinary-drug-stub}} |
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{{Hallucinogen-stub}} |
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Methylergometrine is an agonist of the serotonin 5-HT<sub>2B</sub> receptor and may be linked to ].<ref name="pmid24361689">{{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> |
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{| class="wikitable" |
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|+ {{Nowrap|Activities of methylergometrine at various sites<ref name="PDSPKiDatabase">{{cite web |url=https://pdsp.unc.edu/databases/pdsp.php?testFreeRadio=testFreeRadio&testLigand=Methylergonovine&doQuery=Submit+Query |title=PDSP Database - UNC |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 |url-status=dead}}</ref><ref name="PDSPKiDatabase2">{{cite web |url=https://pdsp.unc.edu/databases/pdsp.php?testFreeRadio=testFreeRadio&testLigand=Methergine&doQuery=Submit+Query |title=PDSP Database - UNC |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 |url-status=dead}}</ref><ref name="BindingDB">{{cite web | last=Liu | first=Tiqing | 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>}} |
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] |
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! Site |
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! Affinity (K<sub>i</sub> ) |
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! Efficacy (E<sub>max</sub> ) |
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! Action |
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|- |
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| ] |
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| 1.5–2.0 |
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| ? |
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| Full agonist |
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|- |
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| ] |
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| 251 |
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| ? |
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| Full agonist |
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|- |
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| ] |
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| 0.86–2.9 |
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| 70 |
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| Partial agonist |
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|- |
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| ] |
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| 89 |
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| ? |
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| Full agonist |
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|- |
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| ] |
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| 31 |
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| ? |
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| Full agonist |
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|- |
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| ] |
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| 0.35–1.1 |
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| ? |
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| Full agonist |
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|- |
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| ] |
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| 0.46–2.2 |
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| ? |
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| Full or partial agonist |
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|- |
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| ] |
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| 4.6–43.7 |
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| ? |
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| Full agonist |
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|- |
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| ] |
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| ? |
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| – |
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| – |
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|- |
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| ] |
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| ? |
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| 24.4<ref name=":0" /> |
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| Full agonist<ref name=":0" /> |
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|- |
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| ] |
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| ? |
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| ? |
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| Full agonist |
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|- |
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| ] |
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| 11–52 |
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| ? |
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| Full agonist |
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|- class="sortbottom" |
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| colspan="4" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Notes:''' All sites are human except 5-HT<sub>1B</sub> (rat) and 5-HT<sub>7</sub> (guinea pig).<ref name="PDSPKiDatabase" /><ref name="PDSPKiDatabase2" /><ref name="BindingDB" /> Additional refs: <ref name="pmid11104741">{{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="GuzmanArmer2020">{{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 | id = 2663 | journal = Neurology | volume = 94 | issue = 15 Supplement | date = April 2020 | doi = 10.1212/WNL.94.15_supplement.2663 | s2cid = 266103427 | url = https://www.xocpharma.com/file.cfm/7/docs/AHS_2019_Poster_1_XocPharma_Final.pdf }}</ref><ref name="OlivierWijngaarden1997">{{cite book| vauthors = Olivier B, van Wijngaarden I, Soudijn W |title=Serotonin Receptors and their Ligands|url=https://books.google.com/books?id=lfo0hGqIex0C&pg=PA149|date=10 July 1997|publisher=Elsevier|isbn=978-0-08-054111-2|pages=149–}}</ref><ref name="Leff1998">{{cite book| vauthors = Leff P |title=Receptor - Based Drug Design|url=https://books.google.com/books?id=YYk04RMvSSUC&pg=PA181|date=10 April 1998|publisher=CRC Press|isbn=978-1-4200-0113-6|pages=181–182}}</ref><ref name="PertzHeich1999">{{cite book|vauthors=Pertz H, Eich E|title=Ergot|chapter=Ergot Alkaloids and their Derivatives as Ligands for Serotoninergic, Dopaminergic, and Adrenergic Receptors|year=1999|pages=432–462|doi=10.1201/9780203304198-21|isbn=9780429219764|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> |
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==Chemistry== |
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Methylergometrine, also known as ''d''-lysergic acid 1-butanolamide, is a ] of the ] and ] classes and is structurally related to ] (''d''-lysergic acid β-propanolamide) and ] (LSD). |
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==References== |
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{{Reflist}} |
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