ERGONOVINE MALEATE

US Previously Marketed

First approved in 1959

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H23N3O2.C4H4O4
Molecular Weight	441.477
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C/C(O)=O.[H][C@@]12CC3=CNC4=C3C(=CC=C4)C1=C[C@H](CN2C)C(=O)N[C@@H](C)CO

InChI

InChIKey=YREISLCRUMOYAY-IIPCNOPRSA-N

InChI=1S/C19H23N3O2.C4H4O4/c1-11(10-23)21-19(24)13-6-15-14-4-3-5-16-18(14)12(8-20-16)7-17(15)22(2)9-13;5-3(6)1-2-4(7)8/h3-6,8,11,13,17,20,23H,7,9-10H2,1-2H3,(H,21,24);1-2H,(H,5,6)(H,7,8)/b;2-1-/t11-,13+,17+;/m0./s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12193527 | http://www.medsafe.govt.nz/profs/Datasheet/d/DBLErgometrineinj.pdf

Ergonovine (also known as ergometrine) is the active water soluble component of ergot of rye. Ergonovine is being used as a maleate salt to prevent or treate postpartum haemorrhage and postabortion haemorrhage. Ergonovine stimulates alpha-adrenergic and serotonin receptors, thus activating contractions of uterine and vascular smooth muscle. Ergonovine may have depressant effect on CNS system as it binds to dopamine receptors.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Adrenergic receptor alpha 64 Target ID: CHEMBL2095203 Sources: http://www.medsafe.govt.nz/profs/Datasheet/d/DBLErgometrineinj.pdf	Partial Agonist 290
Serotonin (5-HT) receptor 34 Target ID: CHEMBL2096904 Sources: http://www.medsafe.govt.nz/profs/Datasheet/d/DBLErgometrineinj.pdf	Partial Agonist 290

Conditions

Condition	Modality	Targets	Highest Phase	Product
Postpartum haemorrhage 4 Sources: http://www.medsafe.govt.nz/profs/Datasheet/d/DBLErgometrineinj.pdf	Preventing		Approved 8429	ERGOMETRINE Approved Use Ergometrine is administered after the delivery of the placenta for the purpose of contracting the uterus in order to prevent or treat postpartum haemorrhage and postabortion haemorrhage due to uterine atony.
Postabortion haemorrhage 4 Sources: http://www.medsafe.govt.nz/profs/Datasheet/d/DBLErgometrineinj.pdf	Preventing		Approved 8429	ERGOMETRINE Approved Use Ergometrine is administered after the delivery of the placenta for the purpose of contracting the uterus in order to prevent or treat postpartum haemorrhage and postabortion haemorrhage due to uterine atony.

C_max

Value	Dose	Co-administered	Analyte	Population
1.07 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8161717/	0.2 mg single, oral dose: 0.2 mg route of administration: Oral experiment type: SINGLE co-administered:		ERGONOVINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
1.69 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8161717/	0.075 mg single, intravenous dose: 0.075 mg route of administration: Intravenous experiment type: SINGLE co-administered:		ERGONOVINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
3.11 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8161717/	0.2 mg single, oral dose: 0.2 mg route of administration: Oral experiment type: SINGLE co-administered:		ERGONOVINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.06 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8161717/	0.075 mg single, intravenous dose: 0.075 mg route of administration: Intravenous experiment type: SINGLE co-administered:		ERGONOVINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
1.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8161717/	0.2 mg single, oral dose: 0.2 mg route of administration: Oral experiment type: SINGLE co-administered:		ERGONOVINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

Doses

Dose	Population	Adverse events
500 ug single, intramuscular (max) Recommended Dose: 500 ug Route: intramuscular Route: single Dose: 500 ug Sources: https://www.medicines.org.uk/emc/product/6265/smpc#CLINICAL_PRECAUTIONS	unhealthy Health Status: unhealthy Condition: Postpartum Haemorrhage Sources: https://www.medicines.org.uk/emc/product/6265/smpc#CLINICAL_PRECAUTIONS	Other AEs: Vasoconstriction, Acute pulmonary oedema... Other AEs: Vasoconstriction Acute pulmonary oedema (rare) Sources: https://www.medicines.org.uk/emc/product/6265/smpc#CLINICAL_PRECAUTIONS

AEs

AE	Significance	Dose	Population
Vasoconstriction		500 ug single, intramuscular (max) Recommended Dose: 500 ug Route: intramuscular Route: single Dose: 500 ug Sources: https://www.medicines.org.uk/emc/product/6265/smpc#CLINICAL_PRECAUTIONS	unhealthy Health Status: unhealthy Condition: Postpartum Haemorrhage Sources: https://www.medicines.org.uk/emc/product/6265/smpc#CLINICAL_PRECAUTIONS
Acute pulmonary oedema	rare	500 ug single, intramuscular (max) Recommended Dose: 500 ug Route: intramuscular Route: single Dose: 500 ug Sources: https://www.medicines.org.uk/emc/product/6265/smpc#CLINICAL_PRECAUTIONS	unhealthy Health Status: unhealthy Condition: Postpartum Haemorrhage Sources: https://www.medicines.org.uk/emc/product/6265/smpc#CLINICAL_PRECAUTIONS

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 activator 80 inhibitor 1587	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 CYP1A2 1524 CYP2A6 707 CYP2C19 1478 CYP2E1 882 OATP1B1 788 OATP1B3 706 CYP19A1 60

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inhibitor 3277 Sources: https://www.scirp.org/html/1-3000180_16854.htm \| https://academic.oup.com/jas/article-abstract/94/suppl_1/32/4700243 \| https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTE5NDQzIn19	inconclusive [IC50 19.9526 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDExOTQ0MyJ9fQ%3D%3D	no [IC50 >10 uM]
CYP19A1 60	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743139#sid=144205575	no
CYP2A6 739	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDExOTQ0MyJ9fQ%3D%3D	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDExOTQ0MyJ9fQ%3D%3D	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDExOTQ0MyJ9fQ%3D%3D	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTE5NDQzIn19	no
CYP2E1 970	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDExOTQ0MyJ9fQ%3D%3D	no
CYP3A4 1925	activator 214 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTE5NDQzIn19	no
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11961113/, http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50390991	weak [Ki 100 uM]
OATP1B1 803	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNjk3NjY4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEyMTMxMzUifX0%3D	yes [Inhibition 10 uM]
OATP1B3 715	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTIxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEyMTMxMzUifX0%3D	yes [Inhibition 10 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://go.drugbank.com/drugs/DB01253, https://pubmed.ncbi.nlm.nih.gov/17948937/, https://www.genome.jp/kegg/drug/br08309.html	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTE5NDQzIn19

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-1440	http://www.3bsc.com/index/pro_info.php?id=55156
AHH Chemical co.,ltd	MT-50822	http://www.ahhchemical.com/product/MT-50822.html
ChemFish Tokyo co.,ltd	443884	http://www.chemfish.co.jp/index.php?id=3965&project=product
ChemMol	99117812	http://www.chemmol.com/chemmol/99117812.html
Finetech	FT-0625687	http://www.finetechnology-ind.com/product/All%20product%20List/60-79-7.html
LGC Standards	DRE-C13201290	https://www.lgcstandards.com/US/en/p/DRE-C13201290
Parchem	26859	http://www.parchem.com/chemical-supplier-distributor/Ergonovine-016859.aspx
Smolecule	S527371	http://www.smolecule.com/products/s527371
Smolecule	S775998	https://www.smolecule.com/products/s775998
THE BioTek	bt-267628	https://www.thebiotek.com/product/inhibitors/bt-267628
TimTec	ST057158	http://www.echemstore.com/st057158-ergonovine-maleate-salt-ergometrine-maleate-salt.html

PubMed

Title	Date	PubMed
Effects of serotonin, dopamine and ergometrine on locomotion in the pulmonate mollusc Helix lucorum.	2001 May	11398751
Major postpartum hemorrhage: survey of maternity units in the United Kingdom.	2002 Aug	12174156
Uterine compression sutures: surgical management of postpartum hemorrhage.	2002 Mar	11864681
St Anthony's fire and living ligatures: a short history of ergometrine.	2002 May 18	12049883
John Chassar Moir (1900-1977) and the discovery of ergometrine.	2002 Sep	12193527
Amphetamine-related acute myocardial infarction due to coronary artery spasm.	2003 Jan-Feb	12587947
Molecular cloning and pharmacological characterization of the guinea pig 5-HT1E receptor.	2004 Jan 26	14744596
Comparative studies on the effect of ergot contaminated feed on performance and health of piglets and chickens.	2005 Apr	16080303
Activity of aqueous extract of the bark of Vitex doniana on uterine muscle response to drugs.	2005 Sep	16220576
Misoprostol in the management of the third stage of labour in the home delivery setting in rural Gambia: a randomised controlled trial.	2005 Sep	16101608
Misoprostol and active management of the third stage of labor.	2006 Aug	16828767
Using clinical audit to improve the quality of obstetric care at the Tibetan Delek Hospital in North India: a longitudinal study.	2006 Jun 7	16759384
Misoprostol in addition to routine treatment of postpartum hemorrhage: a hospital-based randomized-controlled trial in Karachi, Pakistan.	2008 Aug 21	18718007
Bromocriptine, a dopamine D(2) receptor agonist with the structure of the amino acid ergot alkaloids, induces neurite outgrowth in PC12 cells.	2008 Nov 19	18835264
The history of ergot of rye (Claviceps purpurea) II: 1900-1940.	2009 Dec	20509463
Active management of the third stage of labour without controlled cord traction: a randomized non-inferiority controlled trial.	2009 Jan 21	19154621
WITHDRAWN: Active versus expectant management in the third stage of labour.	2009 Jul 8	19588315
A randomized comparison of rectal misoprostol with syntometrine on blood loss in the third stage of labour.	2009 Jun	20043525
Methyl-ergometrine maleate from synchrotron powder diffraction data.	2009 Nov 28	21578950
Argyreia speciosa (Linn. f.) sweet: A comprehensive review.	2010 Jul	22228958
What measured blood loss tells us about postpartum bleeding: a systematic review.	2010 Jun	20406227

Patents

Sample Use Guides

In Vivo Use Guide

Prophylaxis of postpartum haemorrhage and postabortion haemorrhage: the immediate postpartum dose of ergonovine (ergometrine maleate) is 200 ug administered intramuscularly. The injection should not be given until completion of the delivery is assured, and until the possibility of a second twin has been excluded. In an emergency situation, 200 ug may be injected intravenously. IV doses should be given slowly, over a period of at least 1 min. Treatment of postpartum haemorrhage and postabortion haemorrhage: 200 ug may be injected intramuscularly.

Route of Administration: Other

In Vitro Use Guide

Isolated rat uterus was treated with ergometrine at concentrations 0.01, 0.03, 0.1, 0.3, 1, 10 uM and the drug was shown to act as a partial agonist for serotonin receptors.

Name

Type

Language

ERGONOVINE MALEATE

Common Name

English

ERGONOVINE MALEATE [USP MONOGRAPH]

Common Name

English

ERGOMETRINE MALEATE [MART.]

Common Name

English

NSC-93752

Code

English

ERGONOVINE MALEATE [MI]

Common Name

English

ERGONOVINE MALEATE [USP-RS]

Common Name

English

ERGOMETRINE MALEATE [EP MONOGRAPH]

Common Name

English

ERGOMETRINE MALEATE [JAN]

Common Name

English

Ergometrine maleate [WHO-DD]

Common Name

English

ERMETRINE

Brand Name

English

ERGOMETRINE MALEATE

Common Name

English

ERGOMETRINI HYDROGENOMALEAS [WHO-IP LATIN]

Common Name

English

ERGOTRATE MALEATE

Brand Name

English

ERGOMETRINE HYDROGEN MALEATE [WHO-IP]

Common Name

English

9,10-Didehydro-N-[(S)-2-hydroxy-1-methylethyl]-6-methylergoline-8β-carboxamide maleate (1:1) (salt)

Common Name

English

ERGONOVINE MALEATE [VANDF]

Common Name

English

CORNOCENTIN

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C66884