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

Molecular Formula C13H12Cl2O4
Molecular Weight 303.138
Charge 0
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

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
DCPIB is a novel selective blocker of I(Cl,swell) and prevents swelling-induced shortening of guinea-pig atrial action potential duration.
2001 Dec
Quantitative imaging of glutathione in hippocampal neurons and glia in culture using monochlorobimane.
2001 Dec 1
Ethacrynic acid inhibits pancreatic exocrine secretion.
2001 Nov
The glutathione system in alkylator resistance.
2002
Analysis of myogenic mechanisms in renal autoregulation.
2002 Apr
Toxicity of ethacrynic acid in isolated rat hepatocytes.
2002 Apr
Effects of glutathione S-transferase inhibitors on nitroglycerin action in pig isolated coronary arteries.
2002 Dec
Influence of antioxidant depletion on nitrergic relaxation in the pig gastric fundus.
2002 Feb
Differential effects of garlic oil and its three major organosulfur components on the hepatic detoxification system in rats.
2002 Jan 16
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
Nipradilol induces vasodilation of canine isolated posterior ciliary artery via stimulation of the guanylyl cyclase-cGMP pathway.
2002 Jul 26
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
Intra-cochlear administration of dexamethasone attenuates aminoglycoside ototoxicity in the guinea pig.
2002 May
Glutathione S-transferase of the malarial parasite Plasmodium falciparum: characterization of a potential drug target.
2002 May
Influence of temperature, pH, oxygenation, water-type and substrate on biomarker responses in the freshwater clam Corbicula fluminea (Müller).
2002 May
A major human arsenic metabolite, dimethylarsinic acid, requires reduced glutathione to induce apoptosis.
2002 May
Combined effects of cadmium and nickel on testicular xenobiotic metabolizing enzymes in rats.
2002 Nov
Ethacrynic acid rapidly and selectively abolishes blood flow in vessels supplying the lateral wall of the cochlea.
2002 Nov
Interaction between metamizol and tramadol in a model of acute visceral pain in rats.
2003
Characterization of the electrophile binding site and substrate binding mode of the 26-kDa glutathione S-transferase from Schistosoma japonicum.
2003 Apr 1
Dopamine-induced oxidative stress in neurons with glutathione deficit: implication for schizophrenia.
2003 Aug 1
Changes in cell proliferation in rat and guinea pig cochlea after aminoglycoside-induced damage.
2003 Aug 28
Interplay between MRP inhibition and metabolism of MRP inhibitors: the case of curcumin.
2003 Dec
Cytosolic and mitochondrial glutathione in microglial cells are differentially affected by oxidative/nitrosative stress.
2003 Feb
Substrate specificity of mouse aldo-keto reductase AKR7A5.
2003 Feb 1
Ethacrynic acid and the sulfa-sensitive patient.
2003 Jan 13
Engineering a new C-terminal tail in the H-site of human glutathione transferase P1-1: structural and functional consequences.
2003 Jan 3
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 photosensitive vascular smooth muscle store of nitric oxide in mouse aorta: no dependence on expression of endothelial nitric oxide synthase.
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
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
Improved neural representation of vowels in electric stimulation using desynchronizing pulse trains.
2003 Oct
Desynchronization of electrically evoked auditory-nerve activity by high-frequency pulse trains of long duration.
2003 Oct
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
Antioxidant gene therapy can protect hearing and hair cells from ototoxicity.
2004 Feb
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.
Substance Class Chemical
Created
by admin
on Sat Dec 16 17:53:21 GMT 2023
Edited
by admin
on Sat Dec 16 17:53:21 GMT 2023
Record UNII
M5DP350VZV
Record Status Validated (UNII)
Record Version
  • Download
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
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-ATC C03CC01
Created by admin on Sat Dec 16 17:53:22 GMT 2023 , Edited by admin on Sat Dec 16 17:53:22 GMT 2023
LIVERTOX 380
Created by admin on Sat Dec 16 17:53:22 GMT 2023 , Edited by admin on Sat Dec 16 17:53:22 GMT 2023
NDF-RT N0000175590
Created by admin on Sat Dec 16 17:53:22 GMT 2023 , Edited by admin on Sat Dec 16 17:53:22 GMT 2023
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
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
INN
1651
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
CHEBI
4876
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
DRUG CENTRAL
1071
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
DRUG BANK
DB00903
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
NCI_THESAURUS
C485
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
RXCUI
62349
Created by admin on Sat Dec 16 17:53:22 GMT 2023 , Edited by admin on Sat Dec 16 17:53:22 GMT 2023
ALTERNATIVE
DAILYMED
M5DP350VZV
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
NSC
85791
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
RS_ITEM_NUM
1256004
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
ECHA (EC/EINECS)
200-384-1
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
SMS_ID
100000082366
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
IUPHAR
7179
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
MESH
D004976
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
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
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
ChEMBL
CHEMBL456
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
NSC
624008
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
EVMPD
SUB07255MIG
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
PUBCHEM
3278
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
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
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
MERCK INDEX
m5042
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 Merck Index
EPA CompTox
DTXSID3025257
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
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
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DEGRADENT -> PARENT
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