Editing Ergotamine

{{Short description|Chemical compound in the ergot family of alkaloids}}
{{Use dmy dates|date=May 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 443732840
| image = Ergotamine-skeletal.svg
| width = 250
| alt = 
| image2 = Ergotamine ball-and-stick.png
| width2 =
| alt2 = 

<!-- Clinical data -->
| pronounce = 
| tradename = Ergomar, others
| Drugs.com = {{drugs.com|monograph|ergotamine}}
| MedlinePlus = 
| DailyMedID = Ergotamine
| pregnancy_AU = C
| pregnancy_AU_comment = <ref>{{cite web | title=Prescribing medicines in pregnancy database | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/products/medicines/find-information-about-medicine/prescribing-medicines-pregnancy-database | access-date=20 May 2024}}</ref>
| pregnancy_category = US: Contraindicated<ref name="Ergomar FDA label" /><ref>{{cite web | title=Ergotamine (Ergomar) Use During Pregnancy | website=Drugs.com | date=6 May 2024 | url=https://www.drugs.com/pregnancy/ergotamine.html | access-date=20 May 2024}}</ref>
| routes_of_administration = [[Oral administration|Oral]]
| class = 
| ATC_prefix = N02
| ATC_suffix = CA02
| ATC_supplemental = 

<!-- Legal status -->
| legal_AU = Schedule 4
| legal_AU_comment = 
| legal_BR = D1
| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 2023 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=3 August 2023 |access-date=15 August 2023 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=4 April 2023}}</ref>
| legal_CA = Schedule VI
| legal_CA_comment = 
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment = 
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment = 
| legal_UK = POM
| legal_UK_comment = 
| legal_US = Rx-only
| legal_US_comment = <ref name="Ergomar FDA label">{{cite web | title=Ergomar- ergotamine tartrate tablet, orally disintegrating | website=DailyMed | date=8 September 2012 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1bfd4827-5123-4dbb-8f94-7b097f5bfd5c | access-date=20 May 2024}}</ref><ref name="Ergomar sublingual FDA label">{{cite web | title=Ergomar sublingual- ergotamine tartrate tablet | website=DailyMed | date=25 October 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dac9637f-3326-4f25-b7b9-f9f54b738232 | access-date=18 May 2024}}</ref>
| legal_EU = 
| legal_EU_comment = 
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment = 
| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->
| bioavailability = Intravenous: 100%,<ref name="kinetics1">{{cite journal | vauthors = Sanders SW, Haering N, Mosberg H, Jaeger H | title = Pharmacokinetics of ergotamine in healthy volunteers following oral and rectal dosing | journal = European Journal of Clinical Pharmacology | volume = 30 | issue = 3 | pages = 331–334 | date = 1986 | pmid = 3732370 | doi = 10.1007/BF00541538 | s2cid = 37538721 }}</ref> <br />Intramuscular: 47%,<ref name="kinetics2">{{cite book | vauthors = Tfelt-Hansen P, Johnson ES | chapter = Ergotamine | veditors = Olesen J, Tfelt-Hansen P, Welch KM | title = The Headaches | location = New York | publisher = Raven Press | date = 1993 | pages = 313–22 }}</ref><br />Oral: <1%<ref name="pmid6419759">{{cite journal | vauthors = Ibraheem JJ, Paalzow L, Tfelt-Hansen P | title = Low bioavailability of ergotamine tartrate after oral and rectal administration in migraine sufferers | journal = British Journal of Clinical Pharmacology | volume = 16 | issue = 6 | pages = 695–699 | date = December 1983 | pmid = 6419759 | pmc = 1428366 | doi = 10.1111/j.1365-2125.1983.tb02243.x }}</ref> (Enhanced by co-administration of caffeine<ref name="kinetics1" />)
| protein_bound = 
| metabolism = [[Liver]]<ref name="kinetics2" />
| metabolites = 
| onset = 
| elimination_half-life = 2 hours<ref name="kinetics2" />
| duration_of_action = 
| excretion = 90% [[Bile duct]]<ref name="kinetics2" />

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 113-15-5
| CAS_supplemental = 
| PubChem = 8223
| IUPHAR_ligand = 149
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00696
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 7930
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = PR834Q503T
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07906
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 64318
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 442
| NIAID_ChemDB = 
| PDB_ligand = ERM
| synonyms = 2'-Methyl-5'α-benzyl-12'-hydroxy-3',6',18-trioxoergotaman; 9,10α-Dihydro-12'-hydroxy-2'-methyl-5'α-(phenylmethyl)ergotaman-3',6',18-trione

<!-- Chemical data -->
| IUPAC_name = (6a''R'',9''R'')-''N''-((2''R'',5''S'',10a''S'',10b''S'')-5-Benzyl-10b-hydroxy-2-methyl-3,6-dioxooctahydro-2''H''-oxazolo[3,2-''a'']pyrrolo[2,1-''c'']pyrazin-2-yl)-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-''fg'']quinoline-9-carboxamide
| C=33 | H=35 | N=5 | O=5
| SMILES = C[C@@]1(C(=O)N2[C@H](C(=O)N3CCC[C@H]3[C@@]2(O1)O)CC4=CC=CC=C4)NC(=O)[C@H]5CN([C@@H]6CC7=CNC8=CC=CC(=C78)C6=C5)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C33H35N5O5/c1-32(35-29(39)21-15-23-22-10-6-11-24-28(22)20(17-34-24)16-25(23)36(2)18-21)31(41)38-26(14-19-8-4-3-5-9-19)30(40)37-13-7-12-27(37)33(38,42)43-32/h3-6,8-11,15,17,21,25-27,34,42H,7,12-14,16,18H2,1-2H3,(H,35,39)/t21-,25-,26+,27+,32-,33+/m1/s1
| StdInChI_comment = 
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = XCGSFFUVFURLIX-VFGNJEKYSA-N

<!-- Physical data -->
| density = 
| density_notes = 
| melting_point = 
| melting_high = 
| melting_notes = 
| boiling_point = 
| boiling_notes = 
| solubility = 
| sol_units = 
| specific_rotation = 
}}

'''Ergotamine''', sold under the brand name '''Ergomar''' among others, is an [[ergopeptine]] and part of the [[ergot]] family of [[alkaloid]]s; it is structurally and biochemically closely related to [[ergoline]].<ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA397|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=397–}}</ref> It is structurally similar to several [[neurotransmitter]]s, and it [[biological activity|acts]] as a [[vasoconstrictor]]. It is used for acute [[migraine]]s, sometimes with [[caffeine]] as the combination [[ergotamine/caffeine]].<ref name="Cafergot FDA label">{{cite web|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=b4a06de6-f837-43a8-ae7a-aadb38dd2a7d|title= Cafergot- ergotamine tartrate and caffeine tablet, film coated| work = DailyMed | publisher = U.S. National Library of Medicine|url-status=live|archive-url= https://web.archive.org/web/20140116115705/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=b4a06de6-f837-43a8-ae7a-aadb38dd2a7d#DA |archive-date=16 January 2014}}</ref><ref name="Migergot FDA label">{{cite web | title=Migergot- ergotamine tartrate and caffeine suppository | website=DailyMed | date=29 November 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3a31ad0c-7bdd-544b-f5df-a99d04cf541c | access-date=18 May 2024}}</ref>

The drug is a [[binding selectivity|non-selective]] [[receptor modulator|modulator]] or [[agonist]] of [[serotonin receptor]]s and other [[receptor (biochemistry)|receptor]]s.<ref name="pmid23815106" /><ref name="PDSPKiDatabase" /><ref name="KehlerLindskov2025" /> It is [[peripherally selective drug|peripherally selective]] and crosses into the [[brain]] in minimal amounts.<ref name="KehlerLindskov2025">{{cite journal | vauthors = Kehler J, Lindskov MS | title = Are the LSD-analogs lisuride and ergotamine examples of non-hallucinogenic serotonin 5-HT2A receptor agonists? | journal = Journal of Psychopharmacology | pages = 2698811251330741 | date = May 2025 | pmid = 40322975 | doi = 10.1177/02698811251330741 }}</ref>

[[Medicine|Medicinal]] use of ergot fungus began in the 16th century, for the induction of [[childbirth]]; but dosage uncertainty discouraged its use. It has been used to prevent [[post-partum]] [[hemorrhage]] (bleeding after childbirth). It was first isolated from the [[Ergot|ergot fungus]] by [[Arthur Stoll]], at [[Sandoz]] in 1918, and was marketed as Gynergen in 1921.<ref>A. J. Giannini, A. E. Slaby. ''Drugs of Abuse''. Oradell, New Jersey: Medical Economics Books, 1989.</ref>

==Medical uses==
Ergotamine is [[indicated]] as therapy to abort or prevent vascular headache.<ref name="Ergomar FDA label" /><ref name="myths">{{cite journal | vauthors = Zajdel P, Bednarski M, Sapa J, Nowak G | title = Ergotamine and nicergoline - facts and myths | journal = Pharmacological Reports | volume = 67 | issue = 2 | pages = 360–363 | date = April 2015 | pmid = 25712664 | doi = 10.1016/j.pharep.2014.10.010 | s2cid = 22768662 }}</ref>

=== Available forms ===
Ergotamine is available as a [[suppository]] and as a [[tablet (pharmacy)|tablet]], sometimes in [[combination drug|combination]] with [[caffeine]].<ref name="Ergomar FDA label" /><ref name="Ergomar sublingual FDA label" /><ref name="Cafergot FDA label" /><ref name="Migergot FDA label" />

==Contraindications==
Contraindications include: [[atherosclerosis]], [[Buerger's syndrome]], [[coronary artery disease]], hepatic disease, pregnancy, [[pruritus]], [[Raynaud's syndrome]], and renal disease.<ref>{{cite book | vauthors = Giannini AJ | title = Biological Foundations of Clinical Psychiatry | location = Oradell, NJ | publisher = Medical Economics Publishing Co. | date = 1986 }}</ref>
It's also contraindicated if patient is taking [[macrolide antibiotics]] (e.g., [[erythromycin]]), certain HIV [[protease inhibitors]] (e.g., [[ritonavir]], [[nelfinavir]], [[indinavir]]), certain azole antifungals (e.g., [[ketoconazole]], [[itraconazole]], [[voriconazole]]) [[delavirdine]], [[efavirenz]], or a [[5-HT1 agonist|5-HT<sub>1</sub> receptor agonist]] (e.g., [[sumatriptan]]).<ref>{{cite web|title=Ergotamine: Indications, Side Effects, Warnings |url= https://www.drugs.com/cdi/ergotamine.html | work = Drugs.com | access-date=25 March 2017 |url-status=live|archive-url= https://web.archive.org/web/20170325202114/https://www.drugs.com/cdi/ergotamine.html|archive-date=25 March 2017}}</ref>

==Side effects==
Side effects of ergotamine include nausea and vomiting. At higher doses, it can cause raised arterial [[blood pressure]], [[vasoconstriction]] (including [[coronary vasospasm]]) and [[bradycardia]] or [[tachycardia]]. Severe vasoconstriction may cause symptoms of [[intermittent claudication]].<ref>{{cite web|url=https://www.drugs.com/pro/medihaler-ergotamine.html|title=Medihaler Ergotamine|website=[[drugs.com]]|access-date=20 May 2016|url-status=live|archive-url=https://web.archive.org/web/20160401081841/http://www.drugs.com/pro/medihaler-ergotamine.html|archive-date=1 April 2016}}</ref><ref name="myths"/>

==Pharmacology==

===Pharmacodynamics===
Ergotamine interacts with [[serotonin receptor|serotonin]], [[adrenergic receptor|adrenergic]], and [[dopamine receptor]]s.<ref name="pmid23815106">{{cite journal | vauthors = Ramírez Rosas MB, Labruijere S, Villalón CM, Maassen Vandenbrink A | title = Activation of 5-hydroxytryptamine1B/1D/1F receptors as a mechanism of action of antimigraine drugs | journal = Expert Opinion on Pharmacotherapy | volume = 14 | issue = 12 | pages = 1599–1610 | date = August 2013 | pmid = 23815106 | doi = 10.1517/14656566.2013.806487 | s2cid = 22721405 }}</ref><ref name="PDSPKiDatabase" /><ref name="KehlerLindskov2025" /> It is an [[agonist]] of serotonin receptors including the [[serotonin]] [[5-HT1 receptor|5-HT<sub>1</sub>]] and [[5-HT2 receptor|5-HT<sub>2</sub> subtype]]s.<ref name="pmid23815106" /><ref name="KehlerLindskov2025" /> Ergotamine is an agonist of the serotonin [[5-HT2B receptor|5-HT<sub>2B</sub> receptor]] and has been associated with [[cardiac valvulopathy]].<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> Despite acting as a [[potency (pharmacology)|potent]] serotonin [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]] agonist, ergotamine is said to be non-[[hallucinogenic]] similarly to [[lisuride]].<ref name="KehlerLindskov2025" /><ref name="pmid24637012">{{cite journal | vauthors = Karaki S, Becamel C, Murat S, Mannoury la Cour C, Millan MJ, Prézeau L, Bockaert J, Marin P, Vandermoere F | title = Quantitative phosphoproteomics unravels biased phosphorylation of serotonin 2A receptor at Ser280 by hallucinogenic versus nonhallucinogenic agonists | journal = Molecular & Cellular Proteomics | volume = 13 | issue = 5 | pages = 1273–1285 | date = May 2014 | pmid = 24637012 | pmc = 4014284 | doi = 10.1074/mcp.M113.036558 |doi-access=free }}</ref><ref name="HanksGonzález-Maeso2016">{{cite book | vauthors = Hanks J, González-Maeso J |chapter= Molecular and Cellular Basis of Hallucinogen Action | veditors = Preedy VR |title=Neuropathology of Drug Addictions and Substance Misuse |volume=2: Stimulants, Club and Dissociative Drugs, Hallucinogens, Steroids, Inhalants and International Aspects |year=2016 |pages=803–812 |doi=10.1016/B978-0-12-800212-4.00075-3 |isbn=978-0-12-800212-4}}</ref> This has been posited to be due to [[functional selectivity]] at the serotonin 5-HT<sub>2A</sub> receptor.<ref name="pmid24637012" /><ref name="HanksGonzález-Maeso2016" /> However, ergotamine is also [[peripheral selectivity|peripherally selective]], which may instead account for its lack of psychedelic effects.<ref name="KehlerLindskov2025" /><ref name="Canal2018" /><ref name="VerhoeffVisserFerrari1993" />

{| class="wikitable"
|+ {{Nowrap|Activities of ergotamine at various sites<ref name="PDSPKiDatabase">[https://web.archive.org/web/20210413101932/https://pdsp.unc.edu/databases/pdsp.php?testFreeRadio=testFreeRadio&testLigand=Ergotamine&doQuery=Submit+Query PDSP Database – UNC<!-- Bot generated title -->]</ref><ref name="pmid12558771">{{cite journal | vauthors = Silberstein SD, McCrory DC | title = Ergotamine and dihydroergotamine: history, pharmacology, and efficacy | journal = Headache | volume = 43 | issue = 2 | pages = 144–166 | date = February 2003 | pmid = 12558771 | doi = 10.1046/j.1526-4610.2003.03034.x | s2cid = 21356727 }}</ref><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="pmid31418454">{{cite journal | vauthors = Rubio-Beltrán E, Labastida-Ramírez A, Haanes KA, van den Bogaerdt A, Bogers AJ, Zanelli E, Meeus L, Danser AH, Gralinski MR, Senese PB, Johnson KW, Kovalchin J, Villalón CM, MaassenVanDenBrink A | title = Characterization of binding, functional activity, and contractile responses of the selective 5-HT<sub>1F</sub> receptor agonist lasmiditan | journal = British Journal of Pharmacology | volume = 176 | issue = 24 | pages = 4681–4695 | date = December 2019 | pmid = 31418454 | pmc = 6965684 | doi = 10.1111/bph.14832 }}</ref><ref name="pmid20945968">{{cite journal | vauthors = Pytliak M, Vargová V, Mechírová V, Felšöci M | title = Serotonin receptors - from molecular biology to clinical applications | journal = Physiological Research | volume = 60 | issue = 1 | pages = 15–25 | date = 2011 | pmid = 20945968 | doi = 10.33549/physiolres.931903 | doi-access = free }}</ref>}}
! Site
! Affinity (K<sub>i</sub>/IC<sub>50</sub> [nM])
! Efficacy (E<sub>max</sub> [%])
! Action
|-
| [[5-HT1A receptor|5-HT<sub>1A</sub>]]
| 0.17–0.3
| ?
| Full agonist
|-
| [[5-HT1B receptor|5-HT<sub>1B</sub>]]
| 0.3–4.7
| ?
| Agonist
|-
| [[5-HT1D receptor|5-HT<sub>1D</sub>]]
| 0.3–6.0
| ?
| Agonist
|-
| [[5-HT1E receptor|5-HT<sub>1E</sub>]]
| 19–840
| ?
| ?
|-
| [[5-HT1F receptor|5-HT<sub>1F</sub>]]
| 170–171
| ?
| ?
|-
| [[5-HT2A receptor|5-HT<sub>2A</sub>]]
| 0.64–0.97
| ?
| Full agonist
|-
| [[5-HT2B receptor|5-HT<sub>2B</sub>]]
| 1.3–45
| ?
| Partial agonist
|-
| [[5-HT2C receptor|5-HT<sub>2C</sub>]]
| 1.9–9.8
| ?
| Partial agonist
|-
| [[5-HT3 receptor|5-HT<sub>3</sub>]]
| >10,000
| –
| –
|-
| [[5-HT4 receptor|5-HT<sub>4</sub>]]
| 65
| ?
| ?
|-
| [[5-HT5A receptor|5-HT<sub>5A</sub>]]
| 14
| ?
| Agonist
|-
| [[5-HT5B receptor|5-HT<sub>5B</sub>]]
| 3.2–16
| ?
| ?
|-
| [[5-HT6 receptor|5-HT<sub>6</sub>]]
| 12
| ?
| ?
|-
| [[5-HT7 receptor|5-HT<sub>7</sub>]]
| 1,291
| ?
| Agonist
|-
| [[α1A-Adrenergic receptor|α<sub>1A</sub>]]
| 15–>10,000
| –
| –
|-
| [[α1B-Adrenergic receptor|α<sub>1B</sub>]]
| 12–>10,000
| –
| –
|-
| [[α1D-Adrenergic receptor|α<sub>1D</sub>]]
| ?
| ?
| ?
|-
| [[α2A-Adrenergic receptor|α<sub>2A</sub>]]
| 106
| ?
| ?
|-
| [[α2B-Adrenergic receptor|α<sub>2B</sub>]]
| 88
| ?
| ?
|-
| [[α2C-Adrenergic receptor|α<sub>2C</sub>]]
| >10,000
| –
| –
|-
| [[β1-Adrenergic receptor|β<sub>1</sub>]]
| >10,000
| –
| –
|-
| [[β2-Adrenergic receptor|β<sub>2</sub>]]
| >10,000
| –
| –
|-
| [[D1 receptor|D<sub>1</sub>]]
| >10,000
| –
| –
|-
| [[D2 receptor|D<sub>2</sub>]]
| 4.0–>10,000
| –
| Agonist
|-
| [[D3 receptor|D<sub>3</sub>]]
| 3.2–>10,000
| –
| –
|-
| [[D4 receptor|D<sub>4</sub>]]
| 12–>10,000
| –
| –
|-
| [[D5 receptor|D<sub>5</sub>]]
| 170
| ?
| ?
|-
| [[H1 receptor|H<sub>1</sub>]]
| >10,000
| –
| –
|-
| [[H2 receptor|H<sub>2</sub>]]
| >10,000
| –
| –
|-
| [[Muscarinic acetylcholine receptor M1|M<sub>1</sub>]]
| 862
| ?
| ?
|-
| [[Muscarinic acetylcholine receptor M2|M<sub>2</sub>]]
| 911
| ?
| ?
|-
| [[Muscarinic acetylcholine receptor M3|M<sub>3</sub>]]
| >10,000
| –
| –
|-
| [[Muscarinic acetylcholine receptor M4|M<sub>4</sub>]]
| >10,000
| –
| –
|-
| [[Muscarinic acetylcholine receptor M5|M<sub>5</sub>]]
| >10,000
| –
| –
|- class="sortbottom"
| colspan="4" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Notes:''' All receptors are human except 5-HT<sub>5A</sub> (mouse/rat) and 5-HT<sub>5B</sub> (mouse/rat—no human counterpart).<ref name="PDSPKiDatabase" /> No affinity for [[histamine]] [[H1 receptor|H<sub>1</sub>]] or [[H2 receptor|H<sub>2</sub>]], [[cannabinoid receptor|cannabinoid]] [[CB1 receptor|CB<sub>1</sub>]], [[GABA receptor|GABA]], [[glutamate receptor|glutamate]], or [[nicotinic acetylcholine receptor]]s, nor the [[monoamine transporter]]s (all >10,000&nbsp;nM).<ref name="PDSPKiDatabase" />
|}

===Pharmacokinetics===
The [[bioavailability]] of ergotamine is around 2% [[oral administration|orally]], 6% [[rectal administration|rectally]], and 100% by [[intramuscular injection|intramuscular]] or [[intravenous injection]].<ref name="pmid23815106" /> The low oral and rectal bioavailability is due to low [[gastrointestinal tract|gastrointestinal]] [[absorption (pharmacokinetics)|absorption]] and high [[first-pass metabolism]].<ref name="pmid23815106" />

However, ergotamine does not readily cross the [[blood–brain barrier]] and hence is [[peripheral selectivity|peripherally selective]].<ref name="KehlerLindskov2025" /><ref name="Canal2018">{{cite journal | vauthors = Canal CE | title = Serotonergic Psychedelics: Experimental Approaches for Assessing Mechanisms of Action | journal = Handb Exp Pharmacol | series = Handbook of Experimental Pharmacology | volume = 252 | issue = | pages = 227–260 | date = 2018 | pmid = 29532180 | pmc = 6136989 | doi = 10.1007/164_2018_107 | isbn = 978-3-030-10560-0 | url = }}</ref><ref name="VerhoeffVisserFerrari1993">{{cite journal | vauthors = Verhoeff NP, Visser WH, Ferrari MD, Saxena PR, van Royen EA | title = Dopamine D2-receptor imaging with 123I-iodobenzamide SPECT in migraine patients abusing ergotamine: does ergotamine cross the blood brain barrier? | journal = Cephalalgia | volume = 13 | issue = 5 | pages = 325–329 | date = October 1993 | pmid = 8242725 | doi = 10.1046/j.1468-2982.1993.1305325.x | url = }}</ref> This is due to it being an avid [[substrate (biochemistry)|substrate]] for [[P-glycoprotein]] and [[breast cancer resistance protein]] (BCRP).<ref name="KehlerLindskov2025" /> Only minimal amounts of the drug (~1%) cross into the [[brain]].<ref name="KehlerLindskov2025" />

==Biosynthesis==
Ergotamine is a [[secondary metabolite]] ([[natural product]]) and the principal alkaloid produced by the ergot fungus, ''[[Claviceps purpurea]]'', and related fungi in the family [[Clavicipitaceae]].<ref>{{cite web|url=https://pharmaxchange.info/2011/12/pharmacognosy-of-ergot-argot-or-st-anthonys-fire/ |title=Pharmacognosy of Ergot (Argot or St. Anthony's Fire) |date=30 December 2011|website=pharmaxchange.info |url-status=live |archive-url=https://web.archive.org/web/20120717232322/http://pharmaxchange.info/press/2011/12/pharmacognosy-of-ergot-argot-or-st-anthonys-fire/ |archive-date= 17 July 2012 }}</ref>{{Unreliable medical source|date=May 2024}} Its biosynthesis in these fungi requires the [[amino acid]] <small>L</small>-[[tryptophan]] and [[dimethylallyl pyrophosphate]]. These precursor compounds are the substrates for the enzyme, [[tryptophan dimethylallyltransferase]], catalyzing the first step in ergot alkaloid biosynthesis, i.e., the [[prenylation]] of <small>L</small>-tryptophan. Further reactions, involving [[methyltransferase]] and [[oxygenase]] enzymes, yield the [[ergoline]], [[lysergic acid]]. Lysergic acid (LA) is the substrate of ''lysergyl peptide synthetase'', a [[Nonribosomal peptide|nonribosomal peptide synthetase]], which [[covalent]]ly links LA to the amino acids, <small>L</small>-[[alanine]], <small>L</small>-[[proline]], and <small>L</small>-[[phenylalanine]]. Enzyme-catalyzed or spontaneous cyclizations, [[Oxygenation (medicine)|oxygenations]]/[[oxidation]]s, and [[isomerization]]s at selected residues precede, and give rise to, formation of ergotamine.<ref name="Schardl">{{cite book | vauthors = Schardl CL, Panaccione DG, Tudzynski P | title=The Alkaloids: Chemistry and Biology | chapter = Chapter 2 Ergot Alkaloids – Biology and Molecular Biology | journal=The Alkaloids. Chemistry and Biology | volume = 63 | pages = 45–86 | year = 2006 | pmid = 17133714 | doi = 10.1016/S1099-4831(06)63002-2 | isbn = 978-0-12-469563-4 }}</ref>

== Society and culture ==
=== Legal status ===
Ergotamine is a List I regulated chemical in the United States.<ref>{{cite web | title = Lists of: Scheduling Actions, Controlled Substances, Regulated Chemicals | url = https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf | publisher = U.S. Department of Justice | work = Drug Enforcement Administration, Diversion Control Division, Drug & Chemical Evaluation Section | date = February 2020 }}</ref>

== References ==
{{Reflist}}

== External links ==
* {{cite web | title=Ergotamine and caffeine | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a601048.html }}

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