FUROSEMIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H11ClN2O5S
Molecular Weight	330.744
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NS(=O)(=O)C1=CC(C(O)=O)=C(NCC2=CC=CO2)C=C1Cl

InChI

InChIKey=ZZUFCTLCJUWOSV-UHFFFAOYSA-N

InChI=1S/C12H11ClN2O5S/c13-9-5-10(15-6-7-2-1-3-20-7)8(12(16)17)4-11(9)21(14,18)19/h1-5,15H,6H2,(H,16,17)(H2,14,18,19)

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00695
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/pro/furosemide.html

Furosemide, a sulfonamide-type loop diuretic structurally related to bumetanide, is used to manage hypertension and edema associated with congestive heart failure, cirrhosis, and renal disease, including the nephrotic syndrome. Furosemide inhibits water reabsorption in the nephron by blocking the sodium-potassium-chloride cotransporter (NKCC2) in the thick ascending limb of the loop of Henle. This is achieved through competitive inhibition at the chloride binding site on the cotransporter, thus preventing the transport of sodium from the lumen of the loop of Henle into the basolateral interstitium. Consequently, the lumen becomes more hypertonic while the interstitium becomes less hypertonic, which in turn diminishes the osmotic gradient for water reabsorption throughout the nephron. Because the thick ascending limb is responsible for 25% of sodium reabsorption in the nephron, furosemide is a very potent diuretic. Furosemide is sold under the brand name Lasix among others.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Sodium-(potassium)-chloride cotransporter 2 15 Target ID: CHEMBL1874 Sources: http://www.drugbank.ca/drugs/DB00695	Inhibitor 8297
Glucose-6-phosphate 1-dehydrogenase 12 Target ID: P05370 Gene ID: 24377.0 Gene Symbol: G6pdx Target Organism: Rattus norvegicus (Rat) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26758606	Inhibitor 8297	0.13 mM [IC50]
6-phosphogluconate dehydrogenase, decarboxylating 29 Target ID: P85968 Gene ID: 1.00360176E8 Gene Symbol: Pgd Target Organism: Rattus norvegicus (Rat) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26758606	Inhibitor 8297	0.14 mM [IC50]
Glutathione reductase 11 Target ID: CHEMBL3286088 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26758606	Inhibitor 8297	0.08 mM [IC50]
Carbonic anhydrase I 62 Target ID: CHEMBL261 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10713865	Inhibitor 8297
Carbonic anhydrase XIV 22 Target ID: CHEMBL3510 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19119014	Inhibitor 8297	52.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Edema 22 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/016273s068lbl.pdf	Primary		Approved 8429	LASIX Approved Use Edema Furosemide is indicated in adults and pediatric patients for the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephrotic syndrome. Furosemide is particularly useful when an agent with greater diuretic potential is desired. Hypertension Oral Furosemide may be used in adults for the treatment of hypertension alone or in combination with other antihypertensive agents. Launch Date 1966
Hypertension 567 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/016273s068lbl.pdf	Primary		Approved 8429	LASIX Approved Use Edema Furosemide is indicated in adults and pediatric patients for the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephrotic syndrome. Furosemide is particularly useful when an agent with greater diuretic potential is desired. Hypertension Oral Furosemide may be used in adults for the treatment of hypertension alone or in combination with other antihypertensive agents. Launch Date 1966

C_max

Value	Dose	Co-administered	Analyte	Population
1315.34 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12854359	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		FUROSEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
3014.77 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12854359	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		FUROSEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12854359	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		FUROSEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
3.2% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/016273s061lbl.pdf			FUROSEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A 22 OAT1 326 OAT3 339 UGT1A1 418 UGT1A3 422 UGT1A6 307 UGT1A7 236 UGT1A9 380 UGT1A10 291 UGT2B7 389 MRP4 77 BCRP 561 MRP1 107 MRP2 205 P-gp 1537

Drug as victim

Target	Modality	Activity	Clinical evidence
UGT1A9 380	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18541222/ Page: 1.0	major
OAT1 326	substrate 3367 Sources: https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1002/cpt.406#page=9 Page: 9.0	major	yes (co-administration study) Comment: probe drug substrate for renal transporters OAT1 and OAT3; clinical investigation of a probe drug cocktail containing substrates of key drug transporters (digoxin, furosemide, metformin and rosuvastatin) Sources: https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1002/cpt.406#page=9 Page: 9.0
OAT3 339	substrate 3367 Sources: https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1002/cpt.406#page=9 Page: 9.0	major	yes (co-administration study) Comment: probe drug substrate for renal transporters OAT1 and OAT3; clinical investigation of a probe drug cocktail containing substrates of key drug transporters (digoxin, furosemide, metformin and rosuvastatin) Sources: https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1002/cpt.406#page=9 Page: 9.0
MRP1 107	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11948555/ Page: 6.0	no
MRP2 205	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11948555/ Page: 6.0	no
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11948555/ Page: 6.0	no
BCRP 561	substrate 3367 Sources: https://jasn.asnjournals.org/content/jnephrol/18/1/37.full.pdf?with-ds=yes#page=6 Page: 6.0	yes
MRP4 77	substrate 3367 Sources: https://jasn.asnjournals.org/content/jnephrol/18/1/37.full.pdf?with-ds=yes#page=1 Page: 1.0	yes
UGT1A1 418	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18541222/ Page: 1.0	yes
UGT1A10 291	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18541222/ Page: 1.0	yes
UGT1A3 422	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18541222/ Page: 1.0	yes
UGT1A6 307	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18541222/ Page: 1.0	yes
UGT1A7 236	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18541222/ Page: 1.0	yes
UGT2B7 389	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18541222/ Page: 1.0	yes
CYP1A 22	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/19126296/ Page: 1.0	yes	yes (co-administration study) Comment: The time-averaged non-renal clearance (CLNR) of furosemide tended to be faster (but not significantly so) among smokers (3-methylcholanthrene (3-MC) type; a main inducer of CYP1A1/2 Sources: https://pubmed.ncbi.nlm.nih.gov/19126296/ Page: 1.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/15950494/ Page: 8.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:47426	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:47426
ChemicalBook	CB2445739	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2445739
MolPort	MolPort-001-641-065	https://www.molport.com/shop/molecule-link/MolPort-001-641-065
Selleck Chemicals	Furosemide(Lasix)	http://www.selleckchem.com/products/Furosemide(Lasix).html
ZINC	ZINC000000035804	http://zinc15.docking.org/substances/ZINC000000035804
eMolecules	538364	https://www.emolecules.com/cgi-bin/more?vid=538364

PubMed

Title	Date	PubMed
The loop diuretic torasemide interferes with endothelin-1 actions in the aorta of hypertensive rats.	2001	11369815
Effects of loop diuretics on angiotensin II-stimulated vascular smooth muscle cell growth.	2001	11369814
Should celecoxib be contraindicated in patients who are allergic to sulfonamides? Revisiting the meaning of 'sulfa' allergy.	2001	11330653
Maxi K+ channels co-localised with CFTR in the apical membrane of an exocrine gland acinus: possible involvement in secretion.	2001 Apr	11374055
Effect of salicis cortex extract on human platelet aggregation.	2001 Apr	11345689
Improvement in site-specific intestinal absorption of furosemide by Eudragit L100-55.	2001 Apr	11341359
Acute effects of the anti-inflammatory cyclooxygenase-2 selective inhibitor, flosulide, on renal plasma flow and glomerular filtration rate in rats.	2001 Apr	11321358
Furosemide-probenecid interaction as a laboratory exercise for undergraduate education in clinical pharmacology.	2001 Apr	11309551
Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide receptor A-deficient mice.	2001 Apr	11306601
Aspirin inhibits the acute venodilator response to furosemide in patients with chronic heart failure.	2001 Apr	11300428
ATP stimulates calcium-dependent glutamate release from cultured astrocytes.	2001 Apr	11299329
Systemic sclerosis (scleroderma). A case of recovery of cardiomyopathy after vitamin E treatment.	2001 Apr	11292956
Chronic tubulointerstitial nephritis and distal renal tubular acidosis in a patient with frusemide abuse.	2001 Apr	11274294
Renal concentrating defect in mice lacking group IV cytosolic phospholipase A(2).	2001 Apr	11249852
Alternatively spliced isoform of apical Na(+)-K(+)-Cl(-) cotransporter gene encodes a furosemide-sensitive Na(+)-Cl(-)cotransporter.	2001 Apr	11249848
Deterioration of left ventricular chamber performance after bed rest : "cardiovascular deconditioning" or hypovolemia?	2001 Apr 10	11294802
Uptake mechanism of valproic acid in human placental choriocarcinoma cell line (BeWo).	2001 Apr 13	11334847
Distinguishing cochlear pathophysiology in 4-aminopyridine and furosemide treated ears using a nonlinear systems identification technique.	2001 Feb	11248972
Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Frusemide or nitrates in acute left ventricular failure.	2001 Jan	11310465
Self-retaining aural speculum: a valuable aid to middle-ear surgery.	2001 Jan	11233622
Sensitivity of synaptic GABA(A) receptors to allosteric modulators in hippocampal oriens-alveus interneurons.	2001 Jul	11354011
The intracellular localization of the mineralocorticoid receptor is regulated by 11beta-hydroxysteroid dehydrogenase type 2.	2001 Jul 27	11350956
The effects of enalapril-digoxin-diuretic combination therapy on nutritional and anthropometric indices in chronic congestive heart failure: preliminary findings in cardiac cachexia.	2001 Jun	11378008
Urolithiasis in the low birth weight infant: the role and efficacy of extracorporeal shock wave lithotripsy.	2001 Jun	11371971
Angiotensin converting enzyme inhibition worsens the excretory phase of diuretic renography for obstructive hydronephrosis.	2001 Jun	11371966
Supranormal differential renal function is real but may be pathological: assessment by 99m technetium mercaptoacetyltriglycine renal scan of congenital unilateral hydronephrosis.	2001 Jun	11371941
Dynamic characteristics and underlying mechanisms of renal blood flow autoregulation in the conscious dog.	2001 Jun	11352846
Perturbation of the pump-leak balance for Na(+) and K(+) in malaria-infected erythrocytes.	2001 Jun	11350753
Pediatric renal transplantation: anesthesia and perioperative complications.	2001 Mar	11315282
Long-term efficacy of torsemide compared with frusemide in cirrhotic patients with ascites.	2001 Mar	11305520
The appropriateness of drug use in an older nondemented and demented population.	2001 Mar	11300238
Multi-slice CT urography after diuretic injection: initial results.	2001 Mar	11293855
Intraplatelet calcium levels in patients with acute renal failure before and after the administration of loop diuretics.	2001 Mar	11239030
Homogeneous enzyme immunoassay for triiodothyronine in serum.	2001 Mar	11238313
Role of diuretics in the preservation of residual renal function in patients on continuous ambulatory peritoneal dialysis.	2001 Mar	11231370
[Extrarenal effects of furosemide on normal and ischemic cerebral tissue in the rat].	2001 Mar 1-15	11346820
[Generalized edema following insulin treatment of newly diagnosed diabetes mellitus].	2001 Mar 20	11332378
Natriuresis and "dilutional" hyponatremia after infusion of glycine 1.5%.	2001 May	11377153
Taurocholic acid-induced secretion in normal and cystic fibrosis mouse ileum.	2001 May	11370710
Effects of inhalation of albuterol sulphate, ipratroprium bromide and frusemide on breathing mechanics and gas exchange in healthy exercising horses.	2001 May	11352354
Long-term treatment of patients with inappropriate secretion of antidiuretic hormone by the vasopressin receptor antagonist conivaptan, urea, or furosemide.	2001 May	11343672
Chloride channels regulate HIT cell volume but cannot fully account for swelling-induced insulin secretion.	2001 May	11334443
Nephrocalcinosis induced by furosemide in an adult patient with incomplete renal tubular acidosis.	2001 May	11328921
Effects of albumin/furosemide mixtures on responses to furosemide in hypoalbuminemic patients.	2001 May	11316860
Diamidine compounds: selective uptake and targeting in Plasmodium falciparum.	2001 May	11306715
Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney.	2001 May	11306713
Interaction of serotonin and cholecystokinin in the lateral parabrachial nucleus to control sodium intake.	2001 May	11294747
Heterogeneous susceptibility of GABA(A) receptor-mediated IPSCs to depolarization-induced suppression of inhibition in rat hippocampus.	2001 May 1	11313439
Ethanol-induced swelling in neonatal rat primary astrocyte cultures.	2001 May 11	11334801
Fatal portal hypertension, liver failure, and mitochondrial dysfunction after HIV-1 nucleoside analogue-induced hepatitis and lactic acidaemia.	2001 May 5	11356442

Patents

Sample Use Guides

In Vivo Use Guide

The usual initial dose of LASIX is 20 to 80 mg given as a single dose. Ordinarily a prompt diuresis ensues. If needed, the same dose can be administered 6 to 8 hours later or the dose may be increased. The dose may be raised by 20 or 40 mg and given not sooner than 6 to 8 hours after the previous dose until the desired diuretic effect has been obtained. The individually determined single dose should then be given once or twice daily (eg, at 8 am and 2 pm). The dose of LASIX may be carefully titrated up to 600 mg/day in patients with clinically severe edematous states.

Route of Administration: Oral

In Vitro Use Guide

There was a significant reduction in levels of TNF-alpha and IL-6 at a furosemide concentration of 0.5 x 10(-2) M and a reduction in IL-8 levels at 10(-2) M in human peripheral blood mononuclear cells.

Name

Type

Language

FUROSEMIDE

Official Name

English

5-(AMINOSULFONYL)-4-CHLORO-2-((2-FURYLMETHYL)AMINO)BENZOIC ACID

Systematic Name

English

Furosemide [WHO-DD]

Common Name

English

BENZOIC ACID, 5-(AMINOSULFONYL)-4-CHLORO-2-((2-FURANYLMETHYL)AMINO)-

Common Name

English

LOGIRENE

Brand Name

English

FUROSEMIDE [IARC]

Common Name

English

FUROSEMIDE [ORANGE BOOK]

Common Name

English

FUROSEMIDE [EP MONOGRAPH]

Common Name

English

FUROSEMIDE [WHO-IP]

Common Name

English

FUROSEMIDE [VANDF]

Common Name

English

FUROSCIX

Brand Name

English

LB-502

Code

English

OEDEMEX

Common Name

English

FUROSEMIDE [JAN]

Common Name

English

FUROSEMIDUM [WHO-IP LATIN]

Common Name

English

FUROSEMIDE [USP MONOGRAPH]

Common Name

English

FRUSEMIDE

Common Name

English

FUROSEMIDE [GREEN BOOK]

Common Name

English

MARSEMIDE

Common Name

English

furosemide [INN]

Common Name

English

LASIX

Brand Name

English

MIRFAT

Brand Name

English

4-Chloro-N-furfuryl-5-sulfamoylanthranilic acid

Systematic Name

English

NSC-269420

Code

English

FUROSEMIDE [MART.]

Common Name

English

FUROSEMIDE [MI]

Common Name

English

FUROSEMIDE [HSDB]

Common Name

English

FUROSEMIDE [USAN]

Common Name

English

FUROSEMIDE [USP-RS]

Common Name

English

Classification Tree Code System Code

WHO-ESSENTIAL MEDICINES LIST

12.4