ERGOTAMINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C33H35N5O5
Molecular Weight	581.6615
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C[C@@H](C=C2[C@H]1CC3=CNC4=C3C2=CC=C4)C(=O)N[C@]5(C)O[C@@]6(O)[C@@H]7CCCN7C(=O)[C@H](CC8=CC=CC=C8)N6C5=O

InChI

InChIKey=XCGSFFUVFURLIX-VFGNJEKYSA-N

InChI=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

HIDE SMILES / InChI

Molecular Formula	C33H35N5O5
Molecular Weight	581.6615
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	6 / 6
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17149427

The isolation and naming of ergotamine by Stoll occurred in 1925 but the complete elucidation of structure was not achieved until 1951, with synthesis following some 10 years later. Current sources of ergotamine include the isolation from field ergot and fermentation broth, as well as synthesis via coupling of (+)-lysergic acid with the appropriate synthetic peptidic moiety. Ergotamine was introduced into world commerce in 1921, and is currently marketed as its water soluble tartrate salt. Ergotamine is a partial agonist at various tryptaminergic receptors (including the serotonin receptor [5-HT2]) and at various α-adrenergic receptors in blood vessels and various smooth muscles. It is likely that the major activity of ergotamine and related alkaloids is one of agonism at the 5-HT1B/1D receptors, just as with the “triptan” antimigraine compounds. FDA-labeled indications for ergotamine tartrate are in the abortion or prevention of vascular headaches, such as migraine, migraine variant, cluster headache, and histaminic cephalalgia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serotonin 1a (5-HT1a) receptor 177 Target ID: CHEMBL214 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8397171	Agonist 2752	0.34 nM [Ki]
Serotonin 1b (5-HT1b) receptor 45 Target ID: CHEMBL1898 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8397171	Agonist 2752	5.4 nM [Ki]
Serotonin 1d (5-HT1d) receptor 53 Target ID: CHEMBL1983 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8397171	Agonist 2752	0.4 nM [Ki]
Serotonin 1e (5-HT1e) receptor 6 Target ID: CHEMBL2182 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8397171	Agonist 2752	9.4 nM [Ki]
Serotonin 2b (5-HT2b) receptor 60 Target ID: CHEMBL1833 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11104741	Partial Agonist 297	3.0 nM [Ki]
Adrenergic receptor alpha-1 171 Target ID: CHEMBL2094251 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8073910 \| https://www.ncbi.nlm.nih.gov/pubmed/2881518	Antagonist 2849
Adrenergic receptor alpha-2 114 Target ID: CHEMBL2095158 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2881518	Partial Agonist 297

Conditions

Condition	Modality	Highest Phase	Product
Migraine 107 Sources: https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=237166	Primary	Approved 8583	ERGOMAR Approved Use Ergomar® is indicated as therapy to abort or prevent vascular headache, e.g., migraine, migraine variants or a so-called "histaminic cephalalgia". Launch Date 1983
Migraine 107 Sources: http://www.medsafe.govt.nz/profs/Datasheet/c/cafergottab.pdf	Primary	Approved 8583	CAFERGOT Approved Use Treatment of acute attacks of migraine with or without aura in adults.
Migraine 107 Sources: http://www.horizonpharma.com/migergot/	Primary	Approved 8583	MIGERGOT Approved Use MIGERGOT is indicated as therapy to abort or prevent vascular headache, e.g., migraine, migraine variants or so-called “histaminic cephalalgia.” Ergotamine tartrate and caffeine suppositories should only be used for migraine headaches as they are not effective for other types of headaches and they lack analgesic properties. Launch Date 1983

C_max

Value	Dose	Co-administered	Analyte	Population
454 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3732370/	2 mg single, rectal dose: 2 mg route of administration: Rectal experiment type: SINGLE co-administered:		ERGOTAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
21.4 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3732370/	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		ERGOTAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
1216 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3732370/	2 mg single, rectal dose: 2 mg route of administration: Rectal experiment type: SINGLE co-administered:	ERGOTAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
61 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3732370/	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	ERGOTAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4.38 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3932078/	3.89 μg/kg bw single, intravenous dose: 3.89 μg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered:	ERGOTAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
2.04 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3932078/	1.94 μg/kg bw single, intravenous dose: 1.94 μg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered:	ERGOTAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
1.36 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3932078/	1.01 μg/kg bw single, intravenous dose: 1.01 μg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered:	ERGOTAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Analyte	Population
3.35 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3732370/	2 mg single, rectal dose: 2 mg route of administration: Rectal experiment type: SINGLE co-administered:	ERGOTAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.15 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3932078/	3.89 μg/kg bw single, intravenous dose: 3.89 μg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered:	ERGOTAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
2.13 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3932078/	1.94 μg/kg bw single, intravenous dose: 1.94 μg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered:	ERGOTAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
2.08 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3932078/	1.01 μg/kg bw single, intravenous dose: 1.01 μg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered:	ERGOTAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

Doses

Dose	Population	Adverse events
20 mg single, oral Overdose Dose: 20 mg Route: oral Route: single Dose: 20 mg Sources: https://pubmed.ncbi.nlm.nih.gov/23243949	healthy, 21 Health Status: healthy Age Group: 21 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/23243949	Disc. AE: Nausea, Vomiting... AEs leading to discontinuation/dose reduction: Nausea Vomiting (severe) Dizziness Blood pressure decreased Peripheral vasoconstriction Paresthesia Cyanosis peripheral Angina Sources: https://pubmed.ncbi.nlm.nih.gov/23243949
2 mg single, oral Recommended Dose: 2 mg Route: oral Route: single Dose: 2 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1653139	unhealthy, 40+/-10 Health Status: unhealthy Age Group: 40+/-10 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/1653139	Disc. AE: Depression, Vertigo... AEs leading to discontinuation/dose reduction: Depression Vertigo Blurred vision Arrhythmia Hypersensitivity Migraine aggravated Urticaria Dyspnoea Fatigue Tachycardia Vagal reaction Dizziness Tinnitus Sources: https://pubmed.ncbi.nlm.nih.gov/1653139
2 mg single, oral Recommended Dose: 2 mg Route: oral Route: single Dose: 2 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1399547	unhealthy Health Status: unhealthy Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/1399547	Disc. AE: Nausea, Lightheadedness... AEs leading to discontinuation/dose reduction: Nausea (2.4%) Lightheadedness (2.4%) Sources: https://pubmed.ncbi.nlm.nih.gov/1399547

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/18043468/	yes [Ki 13 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC152687/; https://pubmed.ncbi.nlm.nih.gov/24978905/; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313968/	yes		yes (co-administration study) Comment: Coadministration of ergotamine with potent CYP 3A4 inhibitors (ritonavir, nelfinavir, indinavir, erythromycin, clarithromycin, and troleandomycin) has been associated with acute ergot toxicity (ergotism) characterized by vasospasm and ischemia of the extremities Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC152687/; https://pubmed.ncbi.nlm.nih.gov/24978905/; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313968/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:64318	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:64318
ZINC	ZINC000052955754	http://zinc15.docking.org/substances/ZINC000052955754

PubMed

Title	Date	PubMed
FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1.	2013-09-05	23769903
Cloning and characterisation of the human 5-HT5A serotonin receptor.	1994-12-05	7988681
Ergotamine-induced headache can be sustained by sumatriptan daily intake.	1994-10	7828198
Variant angina complicating ergot therapy of migraine.	1994-04	8162760
Ergot induced peripheral vascular insufficiency, non-interventional treatment.	1994-03	7912993
[Ergotamine-induced rectal lesions in asymptomatic patients].	1994	8197748
Ergotamine-induced fetal stress: review of side effects of ergot alkaloids during pregnancy.	1993-09	8282144
[Daily chronic headache in patients with migraine induced by abuse of ergotamine-analgesics: response due to a protocol of outpatient treatment].	1993-08-01	8104438
Two members of a distinct subfamily of 5-hydroxytryptamine receptors differentially expressed in rat brain.	1993-04-15	7682702
Mitral and aortic valve disease associated with ergotamine therapy for migraine. Report of two cases and review of literature.	1990-01	2403780
St. Anthony's fire: a medieval disease in modern times: case history.	1989-10	2802263
[Generalized brain edema and cerebral infarct in ergotamine abuse: imaging by computerized tomography, magnetic resonance tomography and angiography].	1989-09	2591142
[Myocardial infarct caused by an ergotamine tartrate-troleandomycin combination].	1988-09-01	3146787
Amelioration of ergotamine withdrawal symptoms with naproxen.	1987-03	3298163
[Ergotism with cerebral complications. Case report and review of the literature].	1986-04-05	3961460
Ergotamine-induced peripheral ischaemia reversed by oral thymoxamine hydrochloride.	1986-01	2936675
Screening for new compounds with antiherpes activity.	1984-10	6517562
Reversible cerebral arteriopathy associated with the administration of ergot derivatives.	1984-09	6437683
Severe vascular spasm due to erythromycin-ergotamine interaction.	1984-06	6236021
[Ergotamine-induced spasm of the extremities with dorsalis pedis gangrene].	1983-06-10	6410215
[Myocardial infarct during ergotamine medication in a young man with normal coronary arteries].	1983-04-22	6839985
[Ergotism causing peripheral arterial occlusion in the hand].	1983-03	6852679
Ergotamine abuse: results of ergotamine discontinuation, with special reference to the plasma concentrations.	1982-12	7159921
Myocardial infarction following administration of sublingual ergotamine.	1982-09	7105868
Arterial complications of migraine treatment with methysergide and parenteral ergotamine.	1982-07-24	6807440
Acute myocardial infarction induced by ergotamine tartrate: possible role of coronary arterial spasm.	1981-06	6786144
[A case report of acute myocardial infarction induced by ergotamine tartrate (author's transl)].	1981-03	6789432
Reversal of ergotamine-induced arteriospasm by mechanical intra-arterial dilatation.	1980-12-13	6108450
[Non-invasive method for recognition of coronary artery spasm: 201thallium sequential scintigraphy of the myocardium after ergotamine provocation (author's transl)].	1980-04-11	7363818
Angina pectoris and sudden death in the absence of atherosclerosis following ergotamine therapy for migraine.	1979-07	463911
[Bilateral vascular papillitis following ergotamin medication (author's transl)].	1978-11	732190
Adverse effects of ergotamine. Blood circulation disorders--increased headache.	1978-01-10	625738
Myocardial ischaemia in migraine sufferers taking ergotamine.	1978-01	625457
Peripheral vascular spasm due to ergotamine tartrate.	1977-12	271785
[Alarming course of drug-induced ergotism following prolonged use of ergotamine tartatare].	1977-02-18	403449
[Letter: Coronary spasm following ergotamine medication].	1975-09-05	809691
Ischaemic lateral popliteal nerve palsy due to ergot intoxication.	1974-12	4375174
[Ergotamine as a cause of arterial insufficiency].	1974-10-10	4423231
Letter: Ergotamine-induced headaches.	1974-06-29	4852779
Letter: Rebound migraine.	1974-05-11	4827114
Ergotamine-induced venous thrombosis.	1974-04	4449779
[Chronic ergotamine poisoning after migraine treatment].	1974	4408875
Arterial spasm associated with oral ergotamine therapy.	1973-12	4775957
[Acute ischemia of the lower limbs due to ergotamine-induced arteriospasm].	1973-11-30	4792079
Ergotism. Unilateral brachial artery thrombosis secondary to ergotamine tartrate.	1973-06	4712163
[Spasms of the main muscular arteries in the extremities following ingestion of ergotamine-containing drugs].	1973-04-20	4695411
[Severe generalized arteriospasm after a minimal therapeutic dose of ergotamine].	1972-12-14	4347498
[Severe arterial spasms after the use of Ergotamine].	1972-02-08	5015803
Upper limb ischaemia due to ergotamine tartrate.	1970-07	5479581
A case of multiple arterial thromboses after oral contraceptives and ergotamine.	1967-04	6023455

Patents

Sample Use Guides

In Vivo Use Guide

MIGERGOT - ergotamine tartrate and caffeine rectal suppository. One suppository at start of attack; second suppository after 1 hour, if needed for full relief. Two suppositories is the maximum dose for an individual attack. Cafergot (Ergotamine tartrate 1 mg and Caffeine 100 mg Tablets) First attack: The first time Cafergot is taken, an initial dose of 2 Cafergot tablets orally, is recommended. If relief is not obtained within half an hour, a further tablet should be administered; this may be repeated at half-hourly intervals, but the maximum daily dose of 6 tablets should not be exceeded. Subsequent attacks: If the pain persists, take 1 tablet every half an hour up to the maximum daily dose of 6 tablets. The maximum weekly dose is 10 tablets. ERGOMAR SUBLINGUAL- ergotamine tartrate tablet For best results, dosage should start at the first sign of an attack. Early Administration Gives Maximum Effectiveness. At the first sign of an attack or to relieve symptoms after onset of an attack, one 2 mg tablet is placed under the tongue. Another tablet should be taken at half-hour intervals thereafter, if necessary, but dosage must not exceed three tablets in any 24hour period. Total weekly dosage should not exceed five tablets (10 mg) in any one week. Ergomar® Sublingual Tablets should not be used for chronic daily administration.

Route of Administration: Other

In Vitro Use Guide

The bovine anterior pituitary cells were implanted on culture tubes using D-valine minimal essential medium with serum to suppress the overgrowth of fibroblasts and then maintained in L-valine Dulbecco's modified Eagle medium. (3H)-Uridine uptake by these cells was suppressed by ergotamine at a concentration varing from 1-10 uM

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:34:10 GMT 2025` Edited by `admin` on `Mon Mar 31 17:34:10 GMT 2025`
Record UNII	PR834Q503T
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ERGOTAMINE

Official Name

English

NSC-95090

Preferred Name

English

ERGOTAMINE [HSDB]

Common Name

English

Ergotamine [WHO-DD]

Common Name

English

ERGOTAMINE [VANDF]

Common Name

English

ERGOTAMINE [MI]

Common Name

English

ergotamine [INN]

Common Name

English

5??-benzyl-12?-hydroxy-2?-methyl-3?,6?,18-trioxoergotaman

Systematic Name

English

ERGOTAMAN-3',6',18-TRIONE, 12'-HYDROXY-2'-METHYL-5'-(PHENYLMETHYL)-, (5'.ALPHA.)-

Common Name

English

CODERGOCRINE MESILATE IMPURITY C [EP IMPURITY]

Common Name

English

Classification Tree Code System Code

DEA NO.

8676