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Details

Stereochemistry ACHIRAL
Molecular Formula C13H11Cl2O4.Na
Molecular Weight 325.12
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ETHACRYNATE SODIUM

SMILES

[Na+].CCC(=C)C(=O)C1=C(Cl)C(Cl)=C(OCC([O-])=O)C=C1

InChI

InChIKey=CWCSCNSKBSCYCS-UHFFFAOYSA-M
InChI=1S/C13H12Cl2O4.Na/c1-3-7(2)13(18)8-4-5-9(12(15)11(8)14)19-6-10(16)17;/h4-5H,2-3,6H2,1H3,(H,16,17);/q;+1/p-1

HIDE SMILES / InChI

Molecular Formula C13H11Cl2O4
Molecular Weight 302.13
Charge -1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula Na
Molecular Weight 22.9898
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/16092s042,16093s044lbl.pdf

Ethacrynic acid is a monosulfonamyl loop or high ceiling diuretic. Ethacrynic acid acts on the ascending limb of the loop of Henle and on the proximal and distal tubules. Urinary output is usually dose dependent and related to the magnitude of fluid accumulation. Water and electrolyte excretion may be increased several times over that observed with thiazide diuretics, since ethacrynic acid inhibits reabsorption of a much greater proportion of filtered sodium than most other diuretic agents. Therefore, ethacrynic acid is effective in many patients who have significant degrees of renal insufficiency. Ethacrynic acid has little or no effect on glomerular filtration or on renal blood flow, except following pronounced reductions in plasma volume when associated with rapid diuresis. Ethacrynic acid inhibits symport of sodium, potassium, and chloride primarily in the ascending limb of Henle, but also in the proximal and distal tubules. This pharmacological action results in excretion of these ions, increased urinary output, and reduction in extracellular fluid. Diuretics also lower blood pressure initially by reducing plasma and extracellular fluid volume; cardiac output also decreases, explaining its antihypertensive action. Eventually, cardiac output returns to normal with an accompanying decrease in peripheral resistance. Its mode of action does not involve carbonic anhydrase inhibition. Ethacrynic acid is indicated for the treatment of high blood pressure and edema caused by diseases like congestive heart failure, liver failure, and kidney failure.

CNS Activity

Curator's Comment: Ethacrynic acid does not cross the blood-brain barrier

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Glutathione transferases, rat liver
Target ID: P05023|||Q9UJ20
Gene ID: 476.0
Gene Symbol: ATP1A1
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
EDECRIN

Approved Use

EDECRIN is indicated for treatment of edema when an agent with greater diuretic potential than those commonly employed is required. 1. Treatment of the edema associated with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephrotic syndrome. 2. Short-term management of ascites due to malignancy, idiopathic edema, and lymphedema. 3. Short-term management of hospitalized pediatric patients, other than infants, with congenital heart disease or the nephrotic syndrome. 4. Intravenous SODIUM EDECRIN is indicated when a rapid onset of diuresis is desired, e.g., in acute pulmonary edema, or when gastrointestinal absorption is impaired or oral medication is not practicable.

Launch Date

-9.40032E10
Primary
EDECRIN

Approved Use

EDECRIN is indicated for treatment of edema when an agent with greater diuretic potential than those commonly employed is required. 1. Treatment of the edema associated with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephrotic syndrome. 2. Short-term management of ascites due to malignancy, idiopathic edema, and lymphedema. 3. Short-term management of hospitalized pediatric patients, other than infants, with congenital heart disease or the nephrotic syndrome. 4. Intravenous SODIUM EDECRIN is indicated when a rapid onset of diuresis is desired, e.g., in acute pulmonary edema, or when gastrointestinal absorption is impaired or oral medication is not practicable.

Launch Date

-9.40032E10
Doses

Doses

DosePopulationAdverse events​
50 mg 2 times / day multiple, oral
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: edema
Sex: unknown
Sources:
Disc. AE: Diarrhea...
AEs leading to
discontinuation/dose reduction:
Diarrhea (severe)
Sources:
AEs

AEs

AESignificanceDosePopulation
Diarrhea severe
Disc. AE
50 mg 2 times / day multiple, oral
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: edema
Sex: unknown
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer





Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 0.58 uM]
yes [IC50 121 uM]
yes [IC50 29.6 uM]
yes [IC50 8.76 uM]
Drug as victim

Drug as victim

Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Astrocytes as a predominant cellular site of (99m)Tc-HMPAO retention.
2001 Apr
Rat liver microsomal lipid peroxidation produced during the oxidative metabolism of ethacrynic acid.
2001 Apr
Modulation of cisplatin cytotoxicity and cisplatin-induced DNA cross-links in HepG2 cells by regulation of glutathione-related mechanisms.
2001 Apr
Glutathione transferase activities in renal carcinomas and adjacent normal renal tissues: factors influencing renal carcinogenesis induced by xenobiotics.
2001 Jan
Characterization of enzymes participating in carbonyl reduction of 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) in human placenta.
2001 Jan 30
3-Methyleneoxindole: an affinity label of glutathione S-transferase pi which targets tryptophan 38.
2001 Jun 26
Solutol and cremophor products as new additives in suppository formulation.
2002
Chinchilla models of selective cochlear hair cell loss.
2002 Dec
Effects of glutathione S-transferase inhibitors on nitroglycerin action in pig isolated coronary arteries.
2002 Dec
Cellular sensitivity determinants to docetaxel in human gastrointestinal cancers.
2002 Feb
Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance.
2002 Feb 10
Glutathione might exert an important function in caerulein-stimulated amylase release in isolated rat pancreatic acini.
2002 Jan
Differential effects of garlic oil and its three major organosulfur components on the hepatic detoxification system in rats.
2002 Jan 16
Purification and characterization of a novel glutathione S-transferase from Asaphis dichotoma.
2002 Jul 15
Nipradilol induces vasodilation of canine isolated posterior ciliary artery via stimulation of the guanylyl cyclase-cGMP pathway.
2002 Jul 26
Antimicrobial peptides initiate IL-1 beta posttranslational processing: a novel role beyond innate immunity.
2002 Mar 15
Influence of temperature, pH, oxygenation, water-type and substrate on biomarker responses in the freshwater clam Corbicula fluminea (Müller).
2002 May
A possible effect of sulfhydryl reagents on the contractile activity of the rat detrusor muscle.
2002 May 10
Inhibition of the multidrug resistance protein 1 (MRP1) by peptidomimetic glutathione-conjugate analogs.
2002 Nov
Ethacrynic acid rapidly and selectively abolishes blood flow in vessels supplying the lateral wall of the cochlea.
2002 Nov
Characterization of the electrophile binding site and substrate binding mode of the 26-kDa glutathione S-transferase from Schistosoma japonicum.
2003 Apr 1
Changes in cell proliferation in rat and guinea pig cochlea after aminoglycoside-induced damage.
2003 Aug 28
Substrate specificity of mouse aldo-keto reductase AKR7A5.
2003 Feb 1
Exploration of in vitro pro-drug activation and futile cycling by glutathione S-transferases: thiol ester hydrolysis and inhibitor maturation.
2003 Jun 15
Coffee diterpenes prevent benzo[a]pyrene genotoxicity in rat and human culture systems.
2003 Jun 27
A novel Cl- inward-rectifying current in the plasma membrane of the calcifying marine phytoplankton Coccolithus pelagicus.
2003 Mar
Neurotrophic factor effects on oxidative stress-induced neuronal death.
2003 May
Analysis of energy metabolism and mechanism of loop diuretics in the thick ascending limb of Henle's loop in dog kidneys.
2003 May
Ethacrynic acid can be effective for refractory congestive heart failure and ascites.
2003 Nov
Late dosing with ethacrynic acid can reduce gentamicin concentration in perilymph and protect cochlear hair cells.
2003 Nov
Characterization of cell death induced by ethacrynic acid in a human colon cancer cell line DLD-1 and suppression by N-acetyl-L-cysteine.
2003 Oct
Characterization and molecular cloning of a glutathione S-transferase from the whitefly Bemisia tabaci (Hemiptera: Aleyrodidae).
2004 Apr
Glutathione S-transferases and esterases in placenta after normal and pre-eclamptic pregnancies.
2004 Apr
Inhibition of glucose-induced electrical activity in rat pancreatic beta-cells by DCPIB, a selective inhibitor of volume-sensitive anion currents.
2004 Apr 5
Controlled release of ethacrynic acid from poly(lactide-co-glycolide) films for glaucoma treatment.
2004 Aug
The influence of anti-irritants on captopril hydrophilic gel.
2004 Feb
Risk of hospitalization for upper gastrointestinal tract bleeding.
2004 Jan
Co-administration of kanamycin and ethacrynic acid as a deafening method for acute animal experiments.
2004 Jan
Time course of efferent fiber and spiral ganglion cell degeneration following complete hair cell loss in the chinchilla.
2004 Jan 30
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: Can also be used iv: The usual intravenous dose for the average sized adult is 50 mg, or 0.5 to 1.0 mg per kg of body weight. Usually only one dose has been necessary; occasionally a second dose at a new injection site, to avoid possible thrombophlebitis, may be required. A single intravenous dose not exceeding 100 mg has been used in critical situations
Dosage: To Initiate Diuresis In Adults: The smallest dose required to produce gradual weight loss (about 1 to 2 pounds per day) is recommended. Onset of diuresis usually occurs at 50 to 100 mg for adults. After diuresis has been achieved, the minimally effective dose (usually from 50 to 200 mg daily) may be given on a continuous or intermittent dosage schedule.
Route of Administration: Oral
Ethacrynic acid (10uM) induced both apoptosis and necroptosis in primary CLL cells.
Substance Class Chemical
Created
by admin
on Wed Jul 05 23:16:35 UTC 2023
Edited
by admin
on Wed Jul 05 23:16:35 UTC 2023
Record UNII
K41MYV7MPM
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ETHACRYNATE SODIUM
ORANGE BOOK   USAN   USP   VANDF  
USAN  
Official Name English
Etacrynate sodium [WHO-DD]
Common Name English
ETHACRYNATE SODIUM [USP IMPURITY]
Common Name English
ETACRYNATE SODIUM
WHO-DD  
Common Name English
ETHACRYNIC ACID SODIUM SALT [MI]
Common Name English
SODIUM ETACRYNATE [MART.]
Common Name English
ETHACRYNIC ACID SODIUM SALT
MI  
Common Name English
Sodium [2,3-dichloro-4-(2-methylenebutyryl)phenoxy]acetate
Systematic Name English
ETHACRYNATE SODIUM [USAN]
Common Name English
ACETIC ACID, (2,3-DICHLORO-4-(2-METHYLENE-1-OXOBUTYL)PHENOXY)-, SODIUM SALT
Common Name English
ETHACRYNATE SODIUM [VANDF]
Common Name English
ETHACRYNATE SODIUM [ORANGE BOOK]
Common Name English
SODIUM ETHACRYNATE
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C49184
Created by admin on Wed Jul 05 23:16:35 UTC 2023 , Edited by admin on Wed Jul 05 23:16:35 UTC 2023
Code System Code Type Description
NCI_THESAURUS
C47993
Created by admin on Wed Jul 05 23:16:35 UTC 2023 , Edited by admin on Wed Jul 05 23:16:35 UTC 2023
PRIMARY
CAS
6500-81-8
Created by admin on Wed Jul 05 23:16:35 UTC 2023 , Edited by admin on Wed Jul 05 23:16:35 UTC 2023
PRIMARY
PUBCHEM
23668825
Created by admin on Wed Jul 05 23:16:35 UTC 2023 , Edited by admin on Wed Jul 05 23:16:35 UTC 2023
PRIMARY
MERCK INDEX
M5042
Created by admin on Wed Jul 05 23:16:35 UTC 2023 , Edited by admin on Wed Jul 05 23:16:35 UTC 2023
PRIMARY Merck Index
FDA UNII
K41MYV7MPM
Created by admin on Wed Jul 05 23:16:35 UTC 2023 , Edited by admin on Wed Jul 05 23:16:35 UTC 2023
PRIMARY
SMS_ID
100000087295
Created by admin on Wed Jul 05 23:16:35 UTC 2023 , Edited by admin on Wed Jul 05 23:16:35 UTC 2023
PRIMARY
EPA CompTox
DTXSID10215320
Created by admin on Wed Jul 05 23:16:35 UTC 2023 , Edited by admin on Wed Jul 05 23:16:35 UTC 2023
PRIMARY
ChEMBL
CHEMBL456
Created by admin on Wed Jul 05 23:16:35 UTC 2023 , Edited by admin on Wed Jul 05 23:16:35 UTC 2023
PRIMARY
EVMPD
SUB01978MIG
Created by admin on Wed Jul 05 23:16:35 UTC 2023 , Edited by admin on Wed Jul 05 23:16:35 UTC 2023
PRIMARY
RXCUI
4108
Created by admin on Wed Jul 05 23:16:35 UTC 2023 , Edited by admin on Wed Jul 05 23:16:35 UTC 2023
PRIMARY RxNorm
DAILYMED
K41MYV7MPM
Created by admin on Wed Jul 05 23:16:35 UTC 2023 , Edited by admin on Wed Jul 05 23:16:35 UTC 2023
PRIMARY
EVMPD
SUB193938
Created by admin on Wed Jul 05 23:16:35 UTC 2023 , Edited by admin on Wed Jul 05 23:16:35 UTC 2023
ALTERNATIVE
DRUG BANK
DBSALT001225
Created by admin on Wed Jul 05 23:16:35 UTC 2023 , Edited by admin on Wed Jul 05 23:16:35 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY