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
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
DescriptionSources: http://www.drugbank.ca/drugs/DB00903Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/16092s042,16093s044lbl.pdf
Sources: http://www.drugbank.ca/drugs/DB00903
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.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: Glutathione transferases, rat liver Sources: https://www.ncbi.nlm.nih.gov/pubmed/27457758 |
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Target ID: GO:0006927 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26950276 |
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Target ID: P05023|||Q9UJ20 Gene ID: 476.0 Gene Symbol: ATP1A1 Target Organism: Homo sapiens (Human) Sources: http://www.drugbank.ca/drugs/DB00903 |
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Target ID: CHEMBL1874 Sources: http://www.drugbank.ca/drugs/DB00903 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | EDECRIN Approved UseEDECRIN 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 Date1967 |
|||
Primary | EDECRIN Approved UseEDECRIN 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 Date1967 |
Doses
Dose | Population | Adverse 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
AE | Significance | Dose | Population |
---|---|---|---|
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: |
PubMed
Title | Date | PubMed |
---|---|---|
Ethacrynic acid-induced convulsions and brain neurotransmitters in mice. | 1992 Oct 6 |
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The influence of coordinate overexpression of glutathione phase II detoxification gene products on drug resistance. | 2000 Aug |
|
Rat liver microsomal lipid peroxidation produced during the oxidative metabolism of ethacrynic acid. | 2001 Apr |
|
Quantitative imaging of glutathione in hippocampal neurons and glia in culture using monochlorobimane. | 2001 Dec 1 |
|
Glutathione transferase activities in renal carcinomas and adjacent normal renal tissues: factors influencing renal carcinogenesis induced by xenobiotics. | 2001 Jan |
|
Induction of glutathione S-transferase activity and protein expression in brown bullhead (Ameiurus nebulosus) liver by ethoxyquin. | 2001 Jul |
|
Chloride channel antagonists perturb growth and morphology of Neurospora crassa. | 2001 Jul 24 |
|
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 |
|
Ethacrynic acid inhibits pancreatic exocrine secretion. | 2001 Nov |
|
Decreased glutathione S-transferase expression and activity and altered sex steroids in Lake Apopka brown bullheads (Ameiurus nebulosus). | 2001 Nov 12 |
|
Sensitization to the cytotoxicity of melphalan by ethacrynic acid and hyperthermia in drug-sensitive and multidrug-resistant Chinese hamster ovary cells. | 2001 Sep |
|
Purification and characterization of a glutathione S-transferase from the fungus Cunninghamella elegans. | 2001 Sep 25 |
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A putative role for S-nitrosoglutathione as the source of nitric oxide in photorelaxation of the mouse gastric fundus. | 2002 Aug 30 |
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Glutathione might exert an important function in caerulein-stimulated amylase release in isolated rat pancreatic acini. | 2002 Jan |
|
Peptidomimetic glutathione analogues as novel gammaGT stable GST inhibitors. | 2002 Jan |
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Differential effects of garlic oil and its three major organosulfur components on the hepatic detoxification system in rats. | 2002 Jan 16 |
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The organochlorine pesticide residues and antioxidant enzyme activities in human breast tumors: is there any association? | 2002 Mar |
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Glutathione S-transferase of the malarial parasite Plasmodium falciparum: characterization of a potential drug target. | 2002 May |
|
Inhibition of the multidrug resistance protein 1 (MRP1) by peptidomimetic glutathione-conjugate analogs. | 2002 Nov |
|
Interaction between metamizol and tramadol in a model of acute visceral pain in rats. | 2003 |
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Substrate specificity of mouse aldo-keto reductase AKR7A5. | 2003 Feb 1 |
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Engineering a new C-terminal tail in the H-site of human glutathione transferase P1-1: structural and functional consequences. | 2003 Jan 3 |
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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 |
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Continuous administration of antisense oligonucleotides to c-fos reduced the development of seizure susceptibility after ethacrynic acid-induced seizure in mice. | 2003 Sep 25 |
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Controlled release of ethacrynic acid from poly(lactide-co-glycolide) films for glaucoma treatment. | 2004 Aug |
|
Antioxidant gene therapy can protect hearing and hair cells from ototoxicity. | 2004 Feb |
|
Effects of pH and the presence of micelles on the resolution of diuretics by reversed-phase liquid chromatography. | 2004 Jan 2 |
|
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26950276
Ethacrynic acid (10uM) induced both apoptosis and necroptosis in primary CLL cells.
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ACTIVE MOIETY
SUBSTANCE RECORD