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Identification
Name Bendroflumethiazide
Accession Number DB00436 (APRD00666)
Type small molecule
Groups approved
Description

A thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. It has been used in the treatment of familial hyperkalemia, hypertension, edema, and urinary tract disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p810)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Bendrofluazide
  • Bendroflumethazide
  • Bendroflumethiazidum [INN-Latin]
  • Bendroflumetiazida [INN-Spanish]
  • Bendrofumethiazide
  • Benzhydroflumethiazide
  • Benzydroflumethiazide
  • Benzylhydroflumethiazide
  • BHFT
Synonyms
Bendrofluazide
Bendroflumethazide
Bendroflumethiazidum [INN-Latin]
Bendroflumetiazida [INN-Spanish]
Bendrofumethiazide
Benzhydroflumethiazide
Benzydroflumethiazide
Benzylhydroflumethiazide
BHFT
Salts Not Available
Brand names
Name Company
Aprinox
Bentride
Benuron
Benzy-Rodiuran
Benzylrodiuran
Berkozide
Bristuric
Bristuron
Centyl
Corzide
Flumersil
Flumesil
FT 8
Intolex
Livesan
Naigaril
Nateretin
Naturetin
Naturetin-2.5
Naturine
Neo-Naclex
Neo-Rontyl
Niagaril
Nikion
Orsile
Pluryl
Pluryle
Plusuril
Poliuron
Rautrax N
Rauzide
Relan Beta
Repicin
Salural
Salures
Sinesalin
Sodiuretic
Thiazidico
Urlea
First Prev Next Last
Brand mixtures
Brand Name Ingredients
Corzide Tab W Nadolol 40mg Bendroflumethiazide + Nadolol
Corzide Tab W Nadolol 80mg Bendroflumethiazide + Nadolol
Categories
  • Antihypertensive Agents
  • Diuretics
  • Diuretics, Thiazide
  • Sodium Chloride Symporter Inhibitors
CAS number 73-48-3
Weight Average: 421.415
Monoisotopic: 421.037781946
Chemical Formula C15H14F3N3O4S2
InChI Key InChIKey=HDWIHXWEUNVBIY-UHFFFAOYSA-N
InChI
InChI=1S/C15H14F3N3O4S2/c16-15(17,18)10-7-11-13(8-12(10)26(19,22)23)27(24,25)21-14(20-11)6-9-4-2-1-3-5-9/h1-5,7-8,14,20-21H,6H2,(H2,19,22,23)
Plain Text
IUPAC Name
3-benzyl-1,1-dioxo-6-(trifluoromethyl)-3,4-dihydro-2H-1$l^{6},2,4-benzothiadiazine-7-sulfonamide
SMILES
NS(=O)(=O)C1=CC2=C(NC(CC3=CC=CC=C3)NS2(=O)=O)C=C1C(F)(F)F
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzenesulfonamides
  • Sulfanilamides
Substructures
  • Sulfonyls
  • Halogen Derivatives
  • Benzene and Derivatives
  • Benzenesulfonamides
  • Aminals and Derivatives
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Thiadiazines
  • Sulfanilamides
  • Sulfonamides
  • Anilines
Pharmacology
Indication For the treatment of high blood pressure and management of edema related to heart failure.
Pharmacodynamics Bendroflumethiazide, a thiazide diuretic, removes excess water from the body by increasing how often you urinate (pass water) and also widens the blood vessels which helps to reduce blood pressure. It inhibits Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.
Mechanism of action As a diuretic, bendroflumethiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like bendroflumethiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of bendroflumethiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.
Absorption Absorbed relatively rapidly after oral administration
Volume of distribution Not Available
Protein binding 96%
Metabolism Not Available
Route of elimination Not Available
Half life 8.5 hours
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00090 Bendroflumethiazide Pathway SMP00090
Pharmacoeconomics
Manufacturers
  • Apothecon inc div bristol myers squibb
Packagers
Dosage forms Not Available
Prices
Unit description Cost Unit
Bendroflumethiazide powder 45.0 USD g
Corzide 80-5 tablet 4.29 USD tablet
Corzide 40-5 mg tablet 3.46 USD tablet
Corzide 40-5 tablet 3.35 USD tablet
Corzide 80-5 mg tablet 3.23 USD tablet
Patents Not Available
Properties
State solid
Melting point 221-223 oC
Experimental Properties
Property Value Source
water solubility 108 mg/L PhysProp
logP 1.7 PhysProp
logS -3.59 [ADME Research, USCD] PhysProp
pKa 8.5 Various sources
Predicted Properties
Property Value Source
water solubility 2.14e-01 g/l ALOGPS
logP 1.83 ALOGPS
logP 1.7 ChemAxon Molconvert
logS -3.3 ALOGPS
pKa 10.1 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 3 ChemAxon Molconvert
polar surface area 118.36 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 93.68 ChemAxon Molconvert
polarizability 36.92 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00650 Link_out
KEGG Compound C07758 Link_out
PubChem Compound 2315 Link_out
PubChem Substance 46508672 Link_out
ChemSpider 2225 Link_out
ChEBI 3013 Link_out
ChEMBL 3013 Link_out
Therapeutic Targets Database DAP000188 Link_out
PharmGKB PA448563 Link_out
Drug Product Database 29343 Link_out
Drugs.com http://www.drugs.com/cdi/bendroflumethiazide.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Bendroflumethiazide Link_out
ATC Codes
  • C03AA01
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (72.8 KB)
Interactions
Drug Interactions
Drug Interaction
Deslanoside Possible electrolyte variations and arrhythmias
Diazoxide Significant hyperglycemic effect
Digitoxin Possible electrolyte variations and arrhythmias
Digoxin Possible electrolyte variations and arrhythmias
Dofetilide Increased risk of cardiotoxicity and arrhythmias
Lithium The thiazide diuretic, bendroflumethiazide, may increase serum levels of lithium.
Trandolapril The thiazide diuretic, Bendroflumethiazide, may increase the hypotensive effect of Trandolapril. Bendroflumethiazide may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Food Interactions
  • Take with food to increase bioavailability.
Targets

1. Solute carrier family 12 member 3

Pharmacological action: yes
Actions: inhibitor

Electrically silent transporter system. Mediates sodium and chloride reabsorption

Organism class: human
UniProt ID: P55017 Link_out
Gene: SLC12A3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Monroy A, Plata C, Hebert SC, Gamba G: Characterization of the thiazide-sensitive Na(+)-Cl(-) cotransporter: a new model for ions and diuretics interaction. Am J Physiol Renal Physiol. 2000 Jul;279(1):F161-9. Pubmed
  3. Vallon V, Rieg T, Ahn SY, Wu W, Eraly SA, Nigam SK: Overlapping in vitro and in vivo specificities of the organic anion transporters OAT1 and OAT3 for loop and thiazide diuretics. Am J Physiol Renal Physiol. 2008 Apr;294(4):F867-73. Epub 2008 Jan 23. Pubmed

2. Calcium-activated potassium channel subunit alpha 1

Pharmacological action: yes
Actions: inducer

Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX)

Organism class: human
UniProt ID: Q12791 Link_out
Gene: KCNMA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tricarico D, Barbieri M, Mele A, Carbonara G, Camerino DC: Carbonic anhydrase inhibitors are specific openers of skeletal muscle BK channel of K+-deficient rats. FASEB J. 2004 Apr;18(6):760-1. Epub 2004 Feb 6. Pubmed

3. Carbonic anhydrase 1

Pharmacological action: unknown
Actions: inhibitor

Reversible hydration of carbon dioxide

Organism class: human
UniProt ID: P00915 Link_out
Gene: CA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

4. Carbonic anhydrase 2

Pharmacological action: unknown
Actions: inhibitor

Reversible hydration of carbon dioxide

Organism class: human
UniProt ID: P00918 Link_out
Gene: CA2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

5. Carbonic anhydrase 4

Pharmacological action: unknown
Actions: inhibitor

Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4

Organism class: human
UniProt ID: P22748 Link_out
Gene: CA4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
Enzymes

1. Thiopurine S-methyltransferase

Actions: inhibitor

Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine

UniProt ID: P51580 Link_out
Gene: TPMT Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lysaa RA, Giverhaug T, Wold HL, Aarbakke J: Inhibition of human thiopurine methyltransferase by furosemide, bendroflumethiazide and trichlormethiazide. Eur J Clin Pharmacol. 1996;49(5):393-6. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 23, 2012 12:56