Bumetanide

Title: Bumetanide
CAS Registry Number: 28395-03-1
CAS Name: 3-(Aminosulfonyl)-5-(butylamino)-4-phenoxybenzoic acid
Additional Names: 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid
Manufacturers' Codes: PF-1593; Ro-10-6338
Trademarks: Bumex (Roche); Burinex (Leo Pharm); Butinat (Gramon); Fontego (Polifarma); Fordiuran (Thomae); Lunetoron (Sankyo)
Molecular Formula: C17H20N2O5S
Molecular Weight: 364.42
Percent Composition: C 56.03%, H 5.53%, N 7.69%, O 21.95%, S 8.80%
Literature References: Prepn: P. W. Feit, DE 1964503 and DE 1964504; idem, US 3806534 (1970, 1970, 1974 all to Lövens Kemiske Fabrik); idem, J. Med. Chem. 14, 432 (1971). Pharmacology: E. H. Oestergaard et al., Arzneim.-Forsch. 22, 66 (1972). HPLC and GC/MS determn in urine: C. Y. Gradeen et al., J. Anal. Toxicol. 14, 123 (1990). Review of pharmacology and therapeutic use: A. Ward, R. C. Heel, Drugs 28, 426-464 (1984). Series of articles on pharmacokinetics and comparative clinical studies in combination therapy: Curr. Ther. Res. 50, Suppl. A, 1-82 (1991). Comprehensive description: P. N. V. Tata et al., Anal. Profiles Drug Subs. Excip. 22, 107-144 (1993).
Properties: Crystals from aq ethanol, mp 230-231°. pK1 3.6, pK2 7.7. Soly (mg/ml): water 0.1; ethanol 30.6; propylene glycol 18.7; dimethylacetamide >500; methanol 76.5; benzene 0.4; benzyl alcohol 21.6; acetone 50.2. Sol in alkaline solns. uv max (water): 260, 220 nm (E1% 18.9, 17.1); (0.1 N NaOH): 326 nm; (methanol): 270, 345 nm. LD50 i.v. in mice: 330 mg/kg (Oestergaard).
Melting point: mp 230-231°
pKa: pK1 3.6, pK2 7.7
Absorption maximum: uv max (water): 260, 220 nm (E1% 18.9, 17.1)
Toxicity data: LD50 i.v. in mice: 330 mg/kg (Oestergaard)
Therap-Cat: Diuretic.
Keywords: Diuretic; Sulfonamide Derivatives.
Bunaftine Bunamidine Bunamiodyl Sodium Bunazosin Bungarotoxins

Bumetanide
Bumetanide structure.svg
Bumetanide ball-and-stick.png
Systematic (IUPAC) name
3-butylamino-4-phenoxy-5-sulfamoyl-benzoic acid
Clinical data
Trade names Bumex
AHFS/Drugs.com monograph
MedlinePlus a684051
Pregnancy cat. B3 (AU) C (US)
Legal status Prescription Only (S4) (AU) POM (UK) -only (US)
Routes oral
Pharmacokinetic data
Bioavailability almost complete (~80%)
Protein binding 97%
Metabolism hepatic
Half-life ~0.8 hours
Excretion renal
Identifiers
CAS number 28395-03-1 YesY
ATC code C03CA02
PubChem CID 2471
DrugBank DB00887
ChemSpider 2377 YesY
UNII 0Y2S3XUQ5H YesY
KEGG D00247 YesY
ChEBI CHEBI:3213 YesY
ChEMBL CHEMBL1072 YesY
Chemical data
Formula C17H20N2O5S 
Mol. mass 364.417 g/mol
 YesY (what is this?)  (verify)

Bumetanide (trade names Bumex or Burinex) is a loop diuretic of the sulfamyl category to treat heart failure. It is often used in people in whom high doses of furosemide are ineffective. It is marketed by Hoffmann-La Roche. The main difference between the two substances is in bioavailability and pharmacodynamic potency. Furosemide is incompletely absorbed in the intestine (60%), and there is substantial inter- and intraindividual differences in bioavailability (range 10-90%). Bumetanide is almost completely absorbed (80%), and the absorption is not altered when it is taken with food. It is said to be a more predictable diuretic, meaning that the predictable absorption is reflected in a more predictable effect.[1]

Bumetanide is 40 times more potent than furosemide (for patients with normal renal function).[1]

In the brain, bumetanide blocks the NKCC1 cation-chloride co-transporter, and thus decreases internal chloride concentration in neurons. In turn, this concentration change makes the action of GABA more hyperpolarizing, which may be useful for treatment of neonatal seizures, that quite often are not responsive to traditional GABA-targeted treatment, such as barbiturates. Bumetanide is therefore currently under evaluation as a prospective antiepileptic drug.[2]