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Identification
NameBendroflumethiazide
Accession NumberDB00436  (APRD00666)
TypeSmall Molecule
GroupsApproved
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
Synonyms
+--3-Benzyl-3,4-dihydro-6-(trifluoromethyl)-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide
6-Trifluoromethyl-3-benzyl-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine 1,1-dioxide
Bendrofluazide
Bendroflumethiazid
Bendrofluméthiazide
Bendroflumethiazidum
Bendroflumetiazida
Benzhydroflumethiazide
External Identifiers
  • BE 724-A
  • FT 81
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Naturetin 5mgtablet5 mgoralSquibb Canada Inc., Division Of Bristol Myers Squibb Canada Inc.1959-12-311999-01-07Canada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
AprinoxSovereign Medical
CentylLEO Pharma
NaturetinNot Available
Neo-NaclexGlaxoSmithKline
SaluresPfizer
Brand mixtures
NameLabellerIngredients
CorzidePfizer Laboratories Div Pfizer Inc
Corzide Tab W Nadolol 40mgSquibb Canada Inc., Division Of Bristol Myers Squibb Canada Inc.
Corzide Tab W Nadolol 80mgSquibb Canada Inc., Division Of Bristol Myers Squibb Canada Inc.
Nadolol and BendroflumethiazideGlobal Pharmaceuticals, Division of Impax Laboratories, Inc.
SaltsNot Available
Categories
UNII5Q52X6ICJI
CAS number73-48-3
WeightAverage: 421.415
Monoisotopic: 421.037781946
Chemical FormulaC15H14F3N3O4S2
InChI KeyInChIKey=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)
IUPAC Name
3-benzyl-1,1-dioxo-6-(trifluoromethyl)-3,4-dihydro-2H-1λ⁶,2,4-benzothiadiazine-7-sulfonamide
SMILES
NS(=O)(=O)C1=CC2=C(NC(CC3=CC=CC=C3)NS2(=O)=O)C=C1C(F)(F)F
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzothiadiazines. These are organic compounds containing a benzene fused to a thiadiazine ring (a six-member ring with two nitrogen atoms and a sulfur atom).
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassThiadiazines
Sub ClassBenzothiadiazines
Direct ParentBenzothiadiazines
Alternative Parents
Substituents
  • Benzothiadiazine
  • Secondary aliphatic/aromatic amine
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Azacycle
  • Secondary amine
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Amine
  • Alkyl halide
  • Alkyl fluoride
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of high blood pressure and management of edema related to heart failure.
PharmacodynamicsBendroflumethiazide, 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 actionAs 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.
AbsorptionAbsorbed relatively rapidly after oral administration
Volume of distributionNot Available
Protein binding96%
MetabolismNot Available
Route of eliminationNot Available
Half life8.5 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9643
Blood Brain Barrier-0.7807
Caco-2 permeable-0.7105
P-glycoprotein substrateNon-substrate0.6048
P-glycoprotein inhibitor INon-inhibitor0.7889
P-glycoprotein inhibitor IINon-inhibitor0.8383
Renal organic cation transporterNon-inhibitor0.8835
CYP450 2C9 substrateNon-substrate0.708
CYP450 2D6 substrateNon-substrate0.8398
CYP450 3A4 substrateNon-substrate0.6596
CYP450 1A2 substrateInhibitor0.8745
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9351
CYP450 2C19 inhibitorNon-inhibitor0.9287
CYP450 3A4 inhibitorNon-inhibitor0.8607
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9081
Ames testNon AMES toxic0.8474
CarcinogenicityNon-carcinogens0.8156
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.0888 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9858
hERG inhibition (predictor II)Non-inhibitor0.8967
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Apothecon inc div bristol myers squibb
Packagers
Dosage forms
FormRouteStrength
Tabletoral
Tabletoral5 mg
Prices
Unit descriptionCostUnit
Bendroflumethiazide powder45.0USD g
Corzide 80-5 tablet4.29USD tablet
Corzide 40-5 mg tablet3.46USD tablet
Corzide 40-5 tablet3.35USD tablet
Corzide 80-5 mg tablet3.23USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point222-223 °CGoldberg, M.; U.S. Patent 3,265,573; August 9, 1966; assigned to E.R. Squibb & Sons, Inc. Lund, F., Lyngby, K. and Godtfredsen, W.O.; U.S. Patent 3,392,168; July 9, 1968; assigned to Lovens Kemiske Fabrik ved A. Kongsted, Denmark.
water solubility108 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP1.89BERTHOD,A ET AL. (1999)
logS-3.59ADME Research, USCD
pKa8.5SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.214 mg/mLALOGPS
logP1.83ALOGPS
logP1.7ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)9.04ChemAxon
pKa (Strongest Basic)-3.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area118.36 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity93.68 m3·mol-1ChemAxon
Polarizability36.92 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Goldberg, M.; U.S. Patent 3,265,573; August 9, 1966; assigned to E.R. Squibb & Sons, Inc. Lund, F., Lyngby, K. and Godtfredsen, W.O.; U.S. Patent 3,392,168; July 9, 1968; assigned
to Lovens Kemiske Fabrik ved A. Kongsted, Denmark.

General ReferencesNot Available
External Links
ATC CodesC03AA01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (72.8 KB)
Interactions
Drug Interactions
Drug
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Bendroflumethiazide.
AcetylcholineThe risk or severity of adverse effects can be increased when Bendroflumethiazide is combined with Acetylcholine.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Bendroflumethiazide.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Bendroflumethiazide.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Bendroflumethiazide.
AlfuzosinBendroflumethiazide may increase the orthostatic hypotensive activities of Alfuzosin.
AlogliptinThe therapeutic efficacy of Alogliptin can be decreased when used in combination with Bendroflumethiazide.
BrimonidineBrimonidine may increase the antihypertensive activities of Bendroflumethiazide.
BuprenorphineThe risk or severity of adverse effects can be increased when Buprenorphine is combined with Bendroflumethiazide.
ButabarbitalButabarbital may increase the orthostatic hypotensive activities of Bendroflumethiazide.
ButethalButethal may increase the orthostatic hypotensive activities of Bendroflumethiazide.
ButorphanolThe risk or severity of adverse effects can be increased when Butorphanol is combined with Bendroflumethiazide.
CabergolineBendroflumethiazide may increase the vasoconstricting activities of Cabergoline.
CaffeineThe risk or severity of adverse effects can be increased when Caffeine is combined with Bendroflumethiazide.
CanagliflozinThe therapeutic efficacy of Canagliflozin can be decreased when used in combination with Bendroflumethiazide.
CarbacholThe risk or severity of adverse effects can be increased when Bendroflumethiazide is combined with Carbachol.
ChlorphenamineThe risk or severity of adverse effects can be increased when Chlorphenamine is combined with Bendroflumethiazide.
ChlorpropamideBendroflumethiazide may increase the hypoglycemic activities of Chlorpropamide.
CodeineThe risk or severity of adverse effects can be increased when Codeine is combined with Bendroflumethiazide.
ColesevelamColesevelam can cause a decrease in the absorption of Bendroflumethiazide resulting in a reduced serum concentration and potentially a decrease in efficacy.
DexketoprofenThe risk or severity of adverse effects can be increased when Dexketoprofen is combined with Bendroflumethiazide.
DigoxinBendroflumethiazide may increase the bradycardic activities of Digoxin.
DihydrocodeineThe risk or severity of adverse effects can be increased when Dihydrocodeine is combined with Bendroflumethiazide.
DihydrotachysterolBendroflumethiazide may increase the hypercalcemic activities of Dihydrotachysterol.
DipivefrinDipivefrin may increase the atrioventricular blocking (AV block) activities of Bendroflumethiazide.
EsmololEsmolol may increase the bradycardic activities of Bendroflumethiazide.
EthanolEthanol may increase the orthostatic hypotensive activities of Bendroflumethiazide.
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Bendroflumethiazide.
FludrocortisoneFludrocortisone may increase the hypokalemic activities of Bendroflumethiazide.
FlunisolideFlunisolide may increase the hypokalemic activities of Bendroflumethiazide.
GliclazideThe therapeutic efficacy of Gliclazide can be decreased when used in combination with Bendroflumethiazide.
GlimepirideThe therapeutic efficacy of Glimepiride can be decreased when used in combination with Bendroflumethiazide.
GliquidoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Bendroflumethiazide.
GlyburideThe therapeutic efficacy of Glyburide can be decreased when used in combination with Bendroflumethiazide.
HeptabarbitalHeptabarbital may increase the orthostatic hypotensive activities of Bendroflumethiazide.
HexobarbitalHexobarbital may increase the orthostatic hypotensive activities of Bendroflumethiazide.
HydrocodoneThe risk or severity of adverse effects can be increased when Hydrocodone is combined with Bendroflumethiazide.
HydromorphoneThe risk or severity of adverse effects can be increased when Hydromorphone is combined with Bendroflumethiazide.
InfliximabInfliximab may decrease the antihypertensive activities of Bendroflumethiazide.
Insulin AspartThe therapeutic efficacy of Insulin Aspart can be decreased when used in combination with Bendroflumethiazide.
Insulin DetemirThe therapeutic efficacy of Insulin Detemir can be decreased when used in combination with Bendroflumethiazide.
Insulin GlargineThe therapeutic efficacy of Insulin Glargine can be decreased when used in combination with Bendroflumethiazide.
Insulin GlulisineThe therapeutic efficacy of Insulin Glulisine can be decreased when used in combination with Bendroflumethiazide.
Insulin LisproThe therapeutic efficacy of Insulin Lispro can be decreased when used in combination with Bendroflumethiazide.
Insulin RegularThe therapeutic efficacy of Insulin Regular can be decreased when used in combination with Bendroflumethiazide.
Insulin, isophaneThe therapeutic efficacy of Insulin, isophane can be decreased when used in combination with Bendroflumethiazide.
LevorphanolThe risk or severity of adverse effects can be increased when Levorphanol is combined with Bendroflumethiazide.
LicoriceLicorice may increase the hypokalemic activities of Bendroflumethiazide.
LidocaineThe serum concentration of Lidocaine can be increased when it is combined with Bendroflumethiazide.
LinagliptinThe therapeutic efficacy of Linagliptin can be decreased when used in combination with Bendroflumethiazide.
LumacaftorThe serum concentration of Bendroflumethiazide can be decreased when it is combined with Lumacaftor.
MetforminThe therapeutic efficacy of Metformin can be decreased when used in combination with Bendroflumethiazide.
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Bendroflumethiazide.
MethohexitalMethohexital may increase the orthostatic hypotensive activities of Bendroflumethiazide.
MidodrineBendroflumethiazide may increase the activities of Midodrine.
MolsidomineMolsidomine may increase the hypotensive activities of Bendroflumethiazide.
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Bendroflumethiazide.
MoxonidineMoxonidine may increase the hypotensive activities of Bendroflumethiazide.
NalbuphineThe risk or severity of adverse effects can be increased when Nalbuphine is combined with Bendroflumethiazide.
NicorandilNicorandil may increase the hypotensive activities of Bendroflumethiazide.
OctreotideOctreotide may increase the bradycardic activities of Bendroflumethiazide.
OrciprenalineBendroflumethiazide may decrease the activities of Orciprenaline.
OxycodoneThe risk or severity of adverse effects can be increased when Oxycodone is combined with Bendroflumethiazide.
OxymorphoneThe risk or severity of adverse effects can be increased when Oxymorphone is combined with Bendroflumethiazide.
ParoxetineParoxetine may increase the activities of Bendroflumethiazide.
PentazocineThe risk or severity of adverse effects can be increased when Pentazocine is combined with Bendroflumethiazide.
PentobarbitalPentobarbital may increase the orthostatic hypotensive activities of Bendroflumethiazide.
PerindoprilBendroflumethiazide may increase the hypotensive activities of Perindopril.
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Bendroflumethiazide.
PhenelzinePhenelzine may increase the orthostatic hypotensive activities of Bendroflumethiazide.
PrazosinBendroflumethiazide may increase the orthostatic hypotensive activities of Prazosin.
PrimidonePrimidone may increase the orthostatic hypotensive activities of Bendroflumethiazide.
ProcyclidineThe serum concentration of Bendroflumethiazide can be increased when it is combined with Procyclidine.
QuinineQuinine may increase the hypotensive activities of Bendroflumethiazide.
RemifentanilThe risk or severity of adverse effects can be increased when Remifentanil is combined with Bendroflumethiazide.
RepaglinideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Bendroflumethiazide.
SaquinavirThe serum concentration of Bendroflumethiazide can be increased when it is combined with Saquinavir.
SaxagliptinThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Bendroflumethiazide.
SecobarbitalSecobarbital may increase the orthostatic hypotensive activities of Bendroflumethiazide.
SufentanilThe risk or severity of adverse effects can be increased when Sufentanil is combined with Bendroflumethiazide.
TacrineTacrine may increase the bradycardic activities of Bendroflumethiazide.
TadalafilTadalafil may increase the antihypertensive activities of Bendroflumethiazide.
TapentadolThe risk or severity of adverse effects can be increased when Tapentadol is combined with Bendroflumethiazide.
TesmilifeneThe serum concentration of Bendroflumethiazide can be decreased when it is combined with Tesmilifene.
TheophyllineBendroflumethiazide may decrease the activities of Theophylline.
TolbutamideThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Bendroflumethiazide.
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Bendroflumethiazide.
TranylcypromineTranylcypromine may increase the orthostatic hypotensive activities of Bendroflumethiazide.
TreprostinilTreprostinil may increase the hypotensive activities of Bendroflumethiazide.
ValsartanThe risk or severity of adverse effects can be increased when Valsartan is combined with Bendroflumethiazide.
VardenafilVardenafil may increase the antihypertensive activities of Bendroflumethiazide.
VerapamilThe serum concentration of Bendroflumethiazide can be increased when it is combined with Verapamil.
VildagliptinThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Bendroflumethiazide.
Food Interactions
  • Take with food to increase bioavailability.

Targets

1. Solute carrier family 12 member 3

Kind: Protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 12 member 3 P55017 Details

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

Kind: Protein

Organism: Human

Pharmacological action: yes

Actions: inducer

Components

Name UniProt ID Details
Calcium-activated potassium channel subunit alpha-1 Q12791 Details

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

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Carbonic anhydrase 1 P00915 Details

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

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Carbonic anhydrase 2 P00918 Details

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

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Carbonic anhydrase 4 P22748 Details

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

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Thiopurine S-methyltransferase P51580 Details

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

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Drug created on June 13, 2005 07:24 / Updated on March 31, 2014 13:39