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targets (5) transporters (6)
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Identification
Name Bumetanide
Accession Number DB00887 (APRD00294)
Type small molecule
Groups approved
Description

A sulfamyl diuretic. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Bumetanida [INN-Spanish]
  • Bumetanidum [INN-Latin]
Brand names
  • Bumex
  • Burine
  • Burinex
  • Fontego
  • Fordiuran
  • Lixil
  • Lunetoron
  • Segurex
Brand name mixtures Not Available
Categories
  • Diuretics
  • Diuretics, Sulfamyl
  • Sodium Potassium Chloride Symporter Inhibitors
CAS number 28395-03-1
Weight Average: 364.416
Monoisotopic: 364.109292450
Chemical Formula C17H20N2O5S
InChI Key InChIKey=MAEIEVLCKWDQJH-UHFFFAOYSA-N
InChI
InChI=1S/C17H20N2O5S/c1-2-3-9-19-14-10-12(17(20)21)11-15(25(18,22)23)16(14)24-13-7-5-4-6-8-13/h4-8,10-11,19H,2-3,9H2,1H3,(H,20,21)(H2,18,22,23)
Plain Text
IUPAC Name
3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid
SMILES
CCCCNC1=C(OC2=CC=CC=C2)C(=CC(=C1)C(O)=O)S(N)(=O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes
  • Aminobenzoates
  • Benzenesulfonamides
  • Sulfanilamides
Substructures
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Acetates
  • Benzoates
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Sulfonyls
  • Ethers
  • Benzene and Derivatives
  • Aminobenzoates
  • Benzenesulfonamides
  • Carboxylic Acids and Derivatives
  • Aromatic compounds
  • Anisoles
  • Sulfanilamides
  • Sulfonamides
  • Benzoyl Derivatives
  • Phenyl Esters
  • Anilines
Pharmacology
Indication For the treatment of edema associated with congestive heart failure, hepatic and renal disease including the nephrotic syndrome.
Pharmacodynamics Bumetanide is a loop diuretic of the sulfamyl category to treat heart failure. It is often used in patients in whom high doses of furosemide are ineffective. There is however no reason not to use bumetanide as a first choice drug. The main difference between the two substances is in bioavailability. It is said to be a more predictable diuretic, meaning that the predictable absorption is reflected in a more predictable effect. Bumetanide is 40 times more potent than furosemide (for patients with normal renal function).
Mechanism of action Bumetanide interferes with renal cAMP and/or inhibits the sodium-potassium ATPase pump. Bumetanide appears to block the active reabsorption of chloride and possibly sodium in the ascending loop of Henle, altering electrolyte transfer in the proximal tubule. This results in excretion of sodium, chloride, and water and, hence, diuresis.
Absorption Bumetanide is completely absorbed (80%), and the absorption is not altered when taken with food. Bioavailability is almost complete.
Volume of distribution Not Available
Protein binding 97%
Metabolism

45% is secreted unchanged. Urinary and biliary metabolites are formed by oxidation of the N-butyl side chain.
Route of elimination Oral administration of carbon-14 labeled Bumex to human volunteers revealed that 81% of the administered radioactivity was excreted in the urine, 45% of it as unchanged drug. Biliary excretion of Bumex amounted to only 2% of the administered dose.
Half life 60-90 minutes
Clearance
  • 0.2 – 1.1 mL/min/kg [preterm and full-term neonates with respiratory disorders]
  • 2.17 mL/min/kg [neonates receiving bumetanide for volume overload]
  • 1.8 +/- 0.3 mL/min/kg [geriatric subjects]
  • 2.9 +/- 0.2 mL/min/kg [younger subjects]
Toxicity Overdosage can lead to acute profound water loss, volume and electrolyte depletion, dehydration, reduction of blood volume and circulatory collapse with a possibility of vascular thrombosis and embolism. Electrolyte depletion may be manifested by weakness, dizziness, mental confusion, anorexia, lethargy, vomiting and cramps. Treatment consists of replacement of fluid and electrolyte losses by careful monitoring of the urine and electrolyte output and serum electrolyte levels.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00088 Bumetanide Pathway SMP00088
Pharmacoeconomics
Manufacturers
  • Baxter healthcare corp anesthesia and critical care
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • Teva parenteral medicines inc
  • Validus pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Sandoz inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Bumex 2 mg tablet 1.65 USD tablet
Bumetanide 2 mg tablet 1.04 USD tablet
Bumex 1 mg tablet 0.98 USD tablet
Bumex 0.5 mg tablet 0.7 USD tablet
Bumetanide 1 mg tablet 0.51 USD tablet
Bumetanide 0.5 mg tablet 0.38 USD tablet
Bumetanide 0.25 mg/ml vial 0.25 USD ml
Patents Not Available
Properties
State solid
Melting point 230-231 oC
Experimental Properties
Property Value Source
water solubility >20 mg/mL (in base) PhysProp
logP 2.6 PhysProp
Predicted Properties
Property Value Source
water solubility 2.57e-02 g/l ALOGPS
logP 3.44 ALOGPS
logP 2.42 ChemAxon Molconvert
logS -4.15 ALOGPS
pKa 9.62 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 3 ChemAxon Molconvert
polar surface area 118.72 ChemAxon Molconvert
rotatable bond count 8 ChemAxon Molconvert
refractivity 95.78 ChemAxon Molconvert
polarizability 37.21 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00247 Link_out
PubChem Compound 2471 Link_out
PubChem Substance 46508147 Link_out
ChemSpider 2377 Link_out
BindingDB 25903 Link_out
ChEBI 3213 Link_out
ChEMBL 3213 Link_out
Therapeutic Targets Database DAP000361 Link_out
PharmGKB PA448682 Link_out
Drug Product Database 728284 Link_out
RxList http://www.rxlist.com/cgi/generic2/bumetan.htm Link_out
Drugs.com http://www.drugs.com/cdi/bumetanide.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/bum1058.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Bumetanide Link_out
ATC Codes
  • C03CA02
AHFS Codes
  • 40:28.08
PDB Entries Not Available
FDA label show (206.1 KB)
MSDS show (72.8 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take with food to reduce irritation.
Targets

1. Solute carrier family 12 member 1

Pharmacological action: yes
Actions: inhibitor

Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume

Organism class: human
UniProt ID: Q13621 Link_out
Gene: SLC12A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Thakker RV: Chloride channels in renal disease. Adv Nephrol Necker Hosp. 1999;29:289-98. Pubmed
  2. Karolyi L, Koch MC, Grzeschik KH, Seyberth HW: The molecular genetic approach to “Bartter’s syndrome”. J Mol Med. 1998 Apr;76(5):317-25. Pubmed
  3. Thakker RV: The role of renal chloride channel mutations in kidney stone disease and nephrocalcinosis. Curr Opin Nephrol Hypertens. 1998 Jul;7(4):385-8. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  5. Long P, Mercer A, Begum R, Stephens GJ, Sihra TS, Jovanovic JN: Nerve Terminal GABAA Receptors Activate Ca2+/Calmodulin-dependent Signaling to Inhibit Voltage-gated Ca2+ Influx and Glutamate Release. J Biol Chem. 2009 Mar 27;284(13):8726-37. Epub 2009 Jan 13. Pubmed

2. Solute carrier family 12 member 2

Pharmacological action: yes
Actions: inhibitor

Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume

Organism class: human
UniProt ID: P55011 Link_out
Gene: SLC12A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Panet R, Marcus M, Atlan H: Overexpression of the Na()/K()/Cl(-) cotransporter gene induces cell proliferation and phenotypic transformation in mouse fibroblasts. J Cell Physiol. 2000 Jan;182(1):109-18. Pubmed
  2. Evans RL, Park K, Turner RJ, Watson GE, Nguyen HV, Dennett MR, Hand AR, Flagella M, Shull GE, Melvin JE: Severe impairment of salivation in Na+/K+/2Cl- cotransporter (NKCC1)-deficient mice. J Biol Chem. 2000 Sep 1;275(35):26720-6. Pubmed
  3. Wall SM, Fischer MP, Mehta P, Hassell KA, Park SJ: Contribution of the Na+-K+-2Cl- cotransporter NKCC1 to Cl- secretion in rat OMCD. Am J Physiol Renal Physiol. 2001 May;280(5):F913-21. Pubmed
  4. Akar F, Jiang G, Paul RJ, O’Neill WC: Contractile regulation of the Na()-K()-2Cl(-) cotransporter in vascular smooth muscle. Am J Physiol Cell Physiol. 2001 Aug;281(2):C579-84. Pubmed
  5. Jiang G, Klein JD, O’Neill WC: Growth factors stimulate the Na-K-2Cl cotransporter NKCC1 through a novel Cl(-)-dependent mechanism. Am J Physiol Cell Physiol. 2001 Dec;281(6):C1948-53. Pubmed

3. Solute carrier family 12 member 4

Pharmacological action: yes
Actions: inhibitor

Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. May be involved in the regulation of basolateral Cl(-) exit in NaCl absorbing epithelia. Isoform 4 has no transport activity

Organism class: human
UniProt ID: Q9UP95 Link_out
Gene: SLC12A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Jean-Xavier C, Pflieger JF, Liabeuf S, Vinay L: Inhibitory postsynaptic potentials in lumbar motoneurons remain depolarizing after neonatal spinal cord transection in the rat. J Neurophysiol. 2006 Nov;96(5):2274-81. Epub 2006 Jun 28. Pubmed
  2. Reid KH, Guo SZ, Iyer VG: Agents which block potassium-chloride cotransport prevent sound-triggered seizures in post-ischemic audiogenic seizure-prone rats. Brain Res. 2000 May 2;864(1):134-7. Pubmed

4. Solute carrier family 12 member 5

Pharmacological action: yes
Actions: inhibitor

Mediates electroneutral potassium-chloride cotransport in mature neurons. Transport occurs under isotonic conditions, but is activated 20-fold by cell swelling. Important for Cl(-) homeostasis in neurons

Organism class: human
UniProt ID: Q9H2X9 Link_out
Gene: SLC12A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Reid KH, Guo SZ, Iyer VG: Agents which block potassium-chloride cotransport prevent sound-triggered seizures in post-ischemic audiogenic seizure-prone rats. Brain Res. 2000 May 2;864(1):134-7. Pubmed

5. Cystic fibrosis transmembrane conductance regulator

Pharmacological action: unknown
Actions: antagonist

Involved in the transport of chloride ions. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the SLC4A7 transporter

Organism class: human
UniProt ID: P13569 Link_out
Gene: CFTR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Reddy MM, Quinton PM: Bumetanide blocks CFTR GCl in the native sweat duct. Am J Physiol. 1999 Jan;276(1 Pt 1):C231-7. Pubmed
Transporters

1. Sodium/bile acid cotransporter

Actions: substrate, inhibitor

The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presence of sodium

UniProt ID: Q14973 Link_out
Gene: SLC10A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hagenbuch B, Stieger B, Foguet M, Lubbert H, Meier PJ: Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10629-33. Pubmed
  2. Platte HD, Honscha W, Schuh K, Petzinger E: Functional characterization of the hepatic sodium-dependent taurocholate transporter stably transfected into an immortalized liver-derived cell line and V79 fibroblasts. Eur J Cell Biol. 1996 May;70(1):54-60. Pubmed

2. Solute carrier family 22 member 6

Actions: inhibitor
UniProt ID: Q4U2R8 Link_out
Gene: hROAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Race JE, Grassl SM, Williams WJ, Holtzman EJ: Molecular cloning and characterization of two novel human renal organic anion transporters (hOAT1 and hOAT3). Biochem Biophys Res Commun. 1999 Feb 16;255(2):508-14. Pubmed
  2. Uwai Y, Saito H, Hashimoto Y, Inui KI: Interaction and transport of thiazide diuretics, loop diuretics, and acetazolamide via rat renal organic anion transporter rOAT1. J Pharmacol Exp Ther. 2000 Oct;295(1):261-5. Pubmed

3. Solute carrier family 22 member 8

Actions: inhibitor

Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone- 3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA)

UniProt ID: Q8TCC7 Link_out
Gene: SLC22A8 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. Pubmed
  2. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. Pubmed

4. Solute carrier family 22 member 11

Actions: inhibitor

Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds

UniProt ID: Q9NSA0 Link_out
Gene: SLC22A11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cha SH, Sekine T, Kusuhara H, Yu E, Kim JY, Kim DK, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta. J Biol Chem. 2000 Feb 11;275(6):4507-12. Pubmed

5. Solute carrier family 22 member 7

Actions: inhibitor

Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha- ketoglutarate

UniProt ID: Q9Y694 Link_out
Gene: SLC22A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Sekine T, Cha SH, Tsuda M, Apiwattanakul N, Nakajima N, Kanai Y, Endou H: Identification of multispecific organic anion transporter 2 expressed predominantly in the liver. FEBS Lett. 1998 Jun 12;429(2):179-82. Pubmed

6. Solute carrier organic anion transporter family member 1A2

Actions: substrate

Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity)

UniProt ID: P46721 Link_out
Gene: SLCO1A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Horz JA, Honscha W, Petzinger E: Bumetanide is not transported by the Ntcp or by the oatp: evidence for a third organic anion transporter in rat liver cells. Biochim Biophys Acta. 1996 Apr 19;1300(2):114-8. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:07

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.