U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C13H12Cl2O4
Molecular Weight 303.138
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ETHACRYNIC ACID

SMILES

CCC(=C)C(=O)C1=C(Cl)C(Cl)=C(OCC(O)=O)C=C1

InChI

InChIKey=AVOLMBLBETYQHX-UHFFFAOYSA-N
InChI=1S/C13H12Cl2O4/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)

HIDE SMILES / InChI

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

1967
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

1967
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
Ethacrynic acid-induced convulsions and brain neurotransmitters in mice.
1992 Oct 6
Overexpression of glutathione S-transferase II and multidrug resistance transport proteins is associated with acquired tolerance to inorganic arsenic.
2001 Aug
Chloride channel antagonists perturb growth and morphology of Neurospora crassa.
2001 Jul 24
Heterologous expression and characterization of alternatively spliced glutathione S-transferases from a single Anopheles gene.
2001 Jul 26
Determination and characterization of diuretics in human urine by liquid chromatography coupled to pneumatically assisted electrospray ionization mass spectrometry.
2001 Jun
Purification and characterization of multiple glutathione S-transferase isozymes from Chironomidae larvae.
2001 Jun
Differential induction of glutathione S-transferases in the clam Ruditapes decussatus exposed to organic compounds.
2001 Mar
Determination and multivariate statistical analysis of biochemical responses to environmental contaminants in feral freshwater fish Leuciscus cephalus, L.
2001 May
Decreased glutathione S-transferase expression and activity and altered sex steroids in Lake Apopka brown bullheads (Ameiurus nebulosus).
2001 Nov 12
Efflux of glutathione conjugate of monochlorobimane from striatal and cortical neurons.
2001 Oct
Sensitization to the cytotoxicity of melphalan by ethacrynic acid and hyperthermia in drug-sensitive and multidrug-resistant Chinese hamster ovary cells.
2001 Sep
Solutol and cremophor products as new additives in suppository formulation.
2002
Toxicity of ethacrynic acid in isolated rat hepatocytes.
2002 Apr
A putative role for S-nitrosoglutathione as the source of nitric oxide in photorelaxation of the mouse gastric fundus.
2002 Aug 30
Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance.
2002 Feb 10
Peptidomimetic glutathione analogues as novel gammaGT stable GST inhibitors.
2002 Jan
Characteristics of the plasma membrane Cl(-)-ATPase of the bream (Abramis brama) brain sensitive to the inhibitory receptor ligands.
2002 Jan-Feb
Disparity between ionic mediators of volume regulation and apoptosis in N1E 115 mouse neuroblastoma cells.
2002 Jul 12
Purification and characterization of a novel glutathione S-transferase from Asaphis dichotoma.
2002 Jul 15
The organochlorine pesticide residues and antioxidant enzyme activities in human breast tumors: is there any association?
2002 Mar
Antimicrobial peptides initiate IL-1 beta posttranslational processing: a novel role beyond innate immunity.
2002 Mar 15
[The role of thiol oxidants in inhibition of pancreatic exocrine secretory function and glutathione].
2002 May
Glutathione S-transferase of the malarial parasite Plasmodium falciparum: characterization of a potential drug target.
2002 May
Ethacrynic acid rapidly and selectively abolishes blood flow in vessels supplying the lateral wall of the cochlea.
2002 Nov
Induction of cytosolic glutathione S-transferases from Atlantic eel (Anguilla Anguilla) after intraperitoneal treatment with polychlorinated biphenyls.
2002 Oct 7
Cloning and expression of a novel Mu class murine glutathione transferase isoenzyme.
2002 Sep 15
Effect of ethacrynic acid on sodium pump alpha isoforms in SH-SY5Y cells.
2003 Apr
Interplay between MRP inhibition and metabolism of MRP inhibitors: the case of curcumin.
2003 Dec
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
Mitochondrial dysfunction and death in motor neurons exposed to the glutathione-depleting agent ethacrynic acid.
2003 Mar 15
Modulation of pumpkin glutathione S-transferases by aldehydes and related compounds.
2003 May
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
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
Continuous administration of antisense oligonucleotides to c-fos reduced the development of seizure susceptibility after ethacrynic acid-induced seizure in mice.
2003 Sep 25
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
Antioxidant gene therapy can protect hearing and hair cells from ototoxicity.
2004 Feb
Risk of hospitalization for upper gastrointestinal tract bleeding.
2004 Jan
Transport of 99mTc-MAG3 via rat renal organic anion transporter 1.
2004 Jan
Co-administration of kanamycin and ethacrynic acid as a deafening method for acute animal experiments.
2004 Jan
Effects of pH and the presence of micelles on the resolution of diuretics by reversed-phase liquid chromatography.
2004 Jan 2
Time course of efferent fiber and spiral ganglion cell degeneration following complete hair cell loss in the chinchilla.
2004 Jan 30
Interactions of human organic anion transporters with diuretics.
2004 Mar
Cellular glutathione prevents cytolethality of monomethylarsonic acid.
2004 Mar 1
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.
Name Type Language
ETHACRYNIC ACID
HSDB   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF  
USAN  
Official Name English
[2,3-Dichloro-4-(2-methylenebutyryl)phenoxy]acetic acid
Systematic Name English
ETACRYNIC ACID [EP IMPURITY]
Common Name English
ETHACRYNIC ACID [USAN]
Common Name English
ETHACRYNIC ACID [HSDB]
Common Name English
Etacrynic acid [WHO-DD]
Common Name English
2-(2,3-DICHLORO-4-(2-METHYLENE-1-OXOBUTYL)PHENOXY)ACETIC ACID
Systematic Name English
MK-595
Code English
4-(METHYLENEBUTYRYL)-2,3-DICHLOROPHENOXY)ACETIC ACID
Common Name English
ETACRYNIC ACID [EP MONOGRAPH]
Common Name English
ACETIC ACID, (2,3-DICHLORO-4-(2-METHYLENE-1-OXOBUTYL)PHENOXY)-
Common Name English
2,3-DICHLORO-4-(2-METHYLENEBUTYRYL)PHENOXY)ACETATE
Common Name English
NSC-85791
Code English
ETHACRYNIC ACID [MI]
Common Name English
etacrynic acid [INN]
Common Name English
ETACRYNIC ACID [MART.]
Common Name English
ETHACRYNIC ACID [VANDF]
Common Name English
ETHACRYNATE
Common Name English
ETHACRYNIC ACID [USP MONOGRAPH]
Common Name English
ETACRYNIC ACID [JAN]
Common Name English
ETHACRYNIC ACID [ORANGE BOOK]
Common Name English
NSC-624008
Code English
EDECRIN
Brand Name English
ETACRYNIC ACID
EP   INN   MART.   WHO-DD  
INN  
Official Name English
Classification Tree Code System Code
NCI_THESAURUS C49184
Created by admin on Sat Dec 16 17:53:22 GMT 2023 , Edited by admin on Sat Dec 16 17:53:22 GMT 2023
WHO-VATC QC03CC01
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WHO-ATC C03CC01
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LIVERTOX 380
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NDF-RT N0000175590
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NDF-RT N0000175366
Created by admin on Sat Dec 16 17:53:22 GMT 2023 , Edited by admin on Sat Dec 16 17:53:22 GMT 2023
Code System Code Type Description
HSDB
2136
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PRIMARY
INN
1651
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PRIMARY
CHEBI
4876
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PRIMARY
DRUG CENTRAL
1071
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PRIMARY
DRUG BANK
DB00903
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PRIMARY
NCI_THESAURUS
C485
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PRIMARY
RXCUI
62349
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ALTERNATIVE
DAILYMED
M5DP350VZV
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PRIMARY
NSC
85791
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PRIMARY
RS_ITEM_NUM
1256004
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PRIMARY
ECHA (EC/EINECS)
200-384-1
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PRIMARY
SMS_ID
100000082366
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PRIMARY
IUPHAR
7179
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PRIMARY
MESH
D004976
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PRIMARY
WIKIPEDIA
ETACRYNIC ACID
Created by admin on Sat Dec 16 17:53:22 GMT 2023 , Edited by admin on Sat Dec 16 17:53:22 GMT 2023
PRIMARY
CAS
58-54-8
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PRIMARY
ChEMBL
CHEMBL456
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PRIMARY
NSC
624008
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PRIMARY
EVMPD
SUB07255MIG
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PRIMARY
PUBCHEM
3278
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PRIMARY
RXCUI
4109
Created by admin on Sat Dec 16 17:53:22 GMT 2023 , Edited by admin on Sat Dec 16 17:53:22 GMT 2023
PRIMARY
FDA UNII
M5DP350VZV
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PRIMARY
MERCK INDEX
m5042
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PRIMARY Merck Index
EPA CompTox
DTXSID3025257
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PRIMARY
LACTMED
Ethacrynic Acid
Created by admin on Sat Dec 16 17:53:22 GMT 2023 , Edited by admin on Sat Dec 16 17:53:22 GMT 2023
PRIMARY