ERGOTAMINE TARTRATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	2C33H35N5O5.C4H6O6
Molecular Weight	1313.4098
Optical Activity	UNSPECIFIED
Defined Stereocenters	14 / 14
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O[C@H]([C@@H](O)C(O)=O)C(O)=O.[H][C@@]12CCCN1C(=O)[C@H](CC3=CC=CC=C3)N4C(=O)[C@](C)(NC(=O)[C@H]5CN(C)[C@]6([H])CC7=CNC8=C7C(=CC=C8)C6=C5)O[C@@]24O.[H][C@@]9%10CCCN9C(=O)[C@H](CC%11=CC=CC=C%11)N%12C(=O)[C@](C)(NC(=O)[C@H]%13CN(C)[C@]%14([H])CC%15=CNC%16=C%15C(=CC=C%16)C%14=C%13)O[C@@]%10%12O

InChI

InChIKey=CJMJLDQKTOJACI-BGQAIRJTSA-N

InChI=1S/2C33H35N5O5.C4H6O6/c2*1-32(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;5-1(3(7)8)2(6)4(9)10/h2*3-6,8-11,15,17,21,25-27,34,42H,7,12-14,16,18H2,1-2H3,(H,35,39);1-2,5-6H,(H,7,8)(H,9,10)/t2*21-,25-,26+,27+,32-,33+;1-,2-/m111/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

Molecular Formula	C4H6O6
Molecular Weight	150.0868
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
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 171 Target ID: CHEMBL214 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8397171	Agonist 2662	0.34 nM [Ki]
Serotonin 1b (5-HT1b) receptor 45 Target ID: CHEMBL1898 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8397171	Agonist 2662	5.4 nM [Ki]
Serotonin 1d (5-HT1d) receptor 52 Target ID: CHEMBL1983 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8397171	Agonist 2662	0.4 nM [Ki]
Serotonin 1e (5-HT1e) receptor 6 Target ID: CHEMBL2182 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8397171	Agonist 2662	9.4 nM [Ki]
Serotonin 2b (5-HT2b) receptor 60 Target ID: CHEMBL1833 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11104741	Partial Agonist 288	3.0 nM [Ki]
Adrenergic receptor alpha-1 169 Target ID: CHEMBL2094251 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8073910 \| https://www.ncbi.nlm.nih.gov/pubmed/2881518	Antagonist 2760
Adrenergic receptor alpha-2 113 Target ID: CHEMBL2095158 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2881518	Partial Agonist 288

Conditions

Condition	Modality	Highest Phase	Product
Migraine 103 Sources: https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=237166	Primary	Approved 8360	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 4.1472E11
Migraine 103 Sources: http://www.medsafe.govt.nz/profs/Datasheet/c/cafergottab.pdf	Primary	Approved 8360	CAFERGOT Approved Use Treatment of acute attacks of migraine with or without aura in adults.
Migraine 103 Sources: http://www.horizonpharma.com/migergot/	Primary	Approved 8360	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 4.33987191E11

C_max

Value	Dose	Co-administered	Analyte	Population
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
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

AUC

Value	Dose	Analyte	Population
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
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
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
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
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

T_1/2

Value	Dose	Analyte	Population
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
2.08 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
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
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

Doses

Dose	Population	Adverse events
20 mg single, oral Overdose Dose: 20 mg Route: oral Route: single Dose: 20 mg Co-administed with:: caffeine, p.o(2000 mg, single) Sources: https://pubmed.ncbi.nlm.nih.gov/23243949	healthy, 21 n = 1 Health Status: healthy Age Group: 21 Sex: F Population Size: 1 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 Co-administed with:: caffeine, p.o(200 mg, single) Sources: https://pubmed.ncbi.nlm.nih.gov/1653139 Page: p.319	unhealthy, 40+/-10 n = 289 Health Status: unhealthy Condition: Migraine Age Group: 40+/-10 Sex: M+F Population Size: 289 Sources: https://pubmed.ncbi.nlm.nih.gov/1653139 Page: p.319	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 Page: p.319
2 mg single, oral Recommended Dose: 2 mg Route: oral Route: single Dose: 2 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1399547 Page: p.2	unhealthy n = 41 Health Status: unhealthy Condition: Migraine Sex: M+F Population Size: 41 Sources: https://pubmed.ncbi.nlm.nih.gov/1399547 Page: p.2	Disc. AE: Nausea, Lightheadedness... AEs leading to discontinuation/dose reduction: Nausea (2.4%) Lightheadedness (2.4%) Sources: https://pubmed.ncbi.nlm.nih.gov/1399547 Page: p.2

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709 inhibitor 1579

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1909	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/18043468/	yes [Ki 13 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1709	substrate 3326 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
A case of multiple arterial thromboses after oral contraceptives and ergotamine.	1967 Apr	6023455
[Severe generalized arteriospasm after a minimal therapeutic dose of ergotamine].	1972 Dec 14	4347498
[Spasms of the main muscular arteries in the extremities following ingestion of ergotamine-containing drugs].	1973 Apr 20	4695411
Arterial spasm associated with oral ergotamine therapy.	1973 Dec	4775957
[Chronic ergotamine poisoning after migraine treatment].	1974	4408875
Ergot-induced vasospasm of the lower extremities treated with epidural anaesthesia.	1975	1209209
[A case of hyposphygmia caused by ergotamine in migraine].	1975 Feb 21	1113911
[Is triacetyl oleandomycin-ergotamine tartrate combination dangerous?].	1975 Nov 8	1081686
Peripheral vascular spasm due to ergotamine tartrate.	1977 Dec	271785
[A case report of acute myocardial infarction induced by ergotamine tartrate (author's transl)].	1981 Mar	6789432
[Myocardial infarct during ergotamine medication in a young man with normal coronary arteries].	1983 Apr 22	6839985
[Ergotism causing peripheral arterial occlusion in the hand].	1983 Mar	6852679
Severe vascular spasm due to erythromycin-ergotamine interaction.	1984 Jun	6236021
Reversible cerebral arteriopathy associated with the administration of ergot derivatives.	1984 Sep	6437683
[Ergotism with cerebral complications. Case report and review of the literature].	1986 Apr 5	3961460
St. Anthony's fire: a medieval disease in modern times: case history.	1989 Oct	2802263
Saint Anthony's fire revisited. Vascular problems associated with migraine medication.	1991 Jan 21	1898754
Tongue necrosis in temporal arteritis provoked by ergotamine.	1992 Dec	1474364
[Migraine caused by ergotamine tartrate dependence].	1992 Jul	1341823
[Ergotamine-induced rectal lesions in asymptomatic patients].	1994	8197748
Cloning and characterisation of the human 5-HT5A serotonin receptor.	1994 Dec 5	7988681
Transcranial Doppler ultrasonographic features during drug withdrawal from drug-induced headache. A transcranial Doppler follow-up study.	1998 Oct	15613180
[Intractable vomiting, convulsions and megaloblastic anemia: anamnesis, key to diagnosis].	1999 Jul 3	10431323
Ergotamine-induced intermittent claudication.	1999 May	10409924
Ventricular fibrillation secondary to ergotamine in a healthy young woman.	1999 Oct	10596308
Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications.	2000 Dec 5	11104741
The influence of ergotamine abuse on psychological and cognitive functioning.	2000 Jun	11037742
2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors.	2000 Mar 9	10715164
Acute tubulo-interstitial nephritis and renal infarction secondary to ergotamine therapy.	2000 Nov	11071983
Ergotamine, dihydroergotamine: current uses and problems.	2001	12463275
Human 5-HT(5) receptors: the 5-HT(5A) receptor is functional but the 5-HT(5B) receptor was lost during mammalian evolution.	2001 Apr 27	11343685
Ergotamine-induced acute vascular insufficiency of the lower limb--a case report.	2001 Mar	11269787
Drug treatment of orthostatic hypotension because of autonomic failure or neurocardiogenic syncope.	2002	14727996
Successful treatment of threatening limb loss ischemia of the upper limb caused by ergotamine. A case report and review of the literature.	2002 Apr	11887064
Fibrotic valvular heart disease subsequent to bromocriptine treatment.	2002 Nov-Dec	12390688
Efficacy and tolerability of prochlorperazine buccal tablets in treatment of acute migraine.	2002 Oct	12390617
[Multifocal brain haemorrhage associated with migraine and medication abuse].	2003 Nov 1-15	14606052
Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors.	2004 Aug	15322733
[Pergolide treatment and cardiac valve pathology: the continuing saga of ergotamine-induced fibrosis].	2004 Jan	14978390
Severe multivalvular heart disease: a new complication of the ergot derivative dopamine agonists.	2004 Jun	15197703
[Transient global amnesia following the use of ergots in the treatment of migraine].	2004 Nov 16-30	15573308
[Valvular heart disease associated with ergotamine].	2005 Jan	15680136
Interactions of metoclopramide and ergotamine with human 5-HT(3A) receptors and human 5-HT reuptake carriers.	2005 Oct	16041395
Concurrent moyamoya disease and Graves' thyrotoxicosis: case report and literature review.	2006 Jun	16871899
Medications associated with probable medication overuse headache reported in a tertiary care headache center over a 15-year period.	2006 May	16643579
Acute coronary syndrome associated with myocardial bridging due to ergotamine treatment for migraine.	2006 Oct 26	16887217
Drugs and valvular heart disease.	2007 Jan 4	17202450
Hypnic headache associated with medication overuse: case report.	2008 Jul	19085181
Drug-induced fibrotic valvular heart disease.	2009 Aug 15	19683643
Pharmacodynamic action and mechanism of volatile oil from Rhizoma Ligustici Chuanxiong Hort. on treating headache.	2009 Jan	19121572

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 `Wed Jul 05 23:05:21 UTC 2023` Edited by `admin` on `Wed Jul 05 23:05:21 UTC 2023`
Record UNII	MRU5XH3B48
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

ERGOTAMINE TARTRATE

Common Name

English

ERGOSTAT

Brand Name

English

ERGOTAMINE TARTRATE [ORANGE BOOK]

Common Name

English

MEDIHALER ERGOTAMINE

Brand Name

English

ERGOTAMINE TARTRATE [USP IMPURITY]

Common Name

English

Ergotamine tartrate [WHO-DD]

Common Name

English

GOTAMINE TARTRATE

Common Name

English

ERGOTAMINE TARTRATE [MART.]

Common Name

English

ERGOTAMINE TARTRATE [VANDF]

Common Name

English

ERGOTAMINE TARTRATE [WHO-IP]

Common Name

English

ERGOTAMINE TARTRATE COMPONENT OF MIGERGOT

Common Name

English

WIGRAINE COMPONENT ERGOTAMINE TARTRATE

Common Name

English

CAFERGOT COMPONENT ERGOTAMINE TARTRATE

Common Name

English

GYNERGEN

Brand Name

English

ERGOTAMINE TARTRATE COMPONENT OF CAFERGOT

Common Name

English

ERGOTAMINE TARTRATE [MI]

Common Name

English

ERGOMAR

Brand Name

English

WIGRETTES

Brand Name

English

ERGOTAMINE TARTRATE [USP-RS]

Common Name

English

ERGOTAMAN-3',6',18-TRIONE, 12'-HYDROXY-2'-METHYL-5'-(PHENYLMETHYL)-, (5'.ALPHA.)-, (R-(R*,R*))-2,3-DIHYDROXYBUTANEDIOATE (2:1) (SALT)

Common Name

English

ERGOTAMINE D-TARTRATE

Common Name

English

LINGRAINE

Brand Name

English

ERGOTAMINE TARTRATE [JAN]

Common Name

English

NSC-41869

Code

English

ERGOTAMINE TARTRATE COMPONENT OF WIGRAINE

Common Name

English

MIGERGOT COMPONENT ERGOTAMINE TARTRATE

Common Name

English

ERGOTAMINE TARTRATE [USP MONOGRAPH]

Common Name

English

ERGOTAMINE BITARTRATE

Common Name

English

ERGOTAMINI TARTRAS [WHO-IP LATIN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C47794