Identification
- Summary
Bendroflumethiazide is a diuretic used to suppress lactation and to treat hypertension and edema.
- Generic Name
- Bendroflumethiazide
- DrugBank Accession Number
- DB00436
- Background
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)
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Bendroflumethiazide (DB00436)
- Weight
- Average: 421.415
Monoisotopic: 421.037781946 - Chemical Formula
- C15H14F3N3O4S2
- 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
- Bendroflumethiazide
- Bendroflumethiazidum
- Bendroflumetiazida
- Benzhydroflumethiazide
- External IDs
- BE 724-A
- FT 81
Pharmacology
- Indication
For the treatment of high blood pressure and management of edema related to heart failure.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to manage High blood pressure (hypertension) Combination Product in combination with: Nadolol (DB01203) •••••••••••• •••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.
Target Actions Organism ASolute carrier family 12 member 3 inhibitorHumans ACalcium-activated potassium channel subunit alpha-1 inducerHumans UCarbonic anhydrase 1 inhibitorHumans UCarbonic anhydrase 2 inhibitorHumans UCarbonic anhydrase 4 inhibitorHumans - 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
- Adverse Effects
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Not Available
- Pathways
Pathway Category Bendroflumethiazide Action Pathway Drug action - Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Bendroflumethiazide may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy. Abaloparatide The risk or severity of adverse effects can be increased when Bendroflumethiazide is combined with Abaloparatide. Abciximab The therapeutic efficacy of Abciximab can be decreased when used in combination with Bendroflumethiazide. Acarbose The therapeutic efficacy of Acarbose can be decreased when used in combination with Bendroflumethiazide. Acebutolol The therapeutic efficacy of Acebutolol can be increased when used in combination with Bendroflumethiazide. - Food Interactions
- Take with food. Food increases bioavailability.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Aprinox (Sovereign Medical) / Centyl (LEO Pharma) / Neo-Naclex (GlaxoSmithKline) / Salures (Pfizer)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Naturetin Tablet 5 mg/1 Oral E.R. Squibb & Sons, L.L.C. 2005-01-01 2006-10-31 US 
Naturetin 5mg Tablet 5 mg Oral Squibb Canada Inc., Division Of Bristol Myers Squibb Canada Inc. 1959-12-31 1999-01-07 Canada 
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Corzide Bendroflumethiazide (5 mg/1) + Nadolol (40 mg/1) Tablet Oral Pfizer Laboratories Div Pfizer Inc 1983-05-25 2019-10-31 US Corzide Bendroflumethiazide (5 mg/1) + Nadolol (40 mg/1) Tablet Oral Monarch Pharmaceuticals, Inc. 2006-10-10 2006-10-10 US Corzide Bendroflumethiazide (5 mg/1) + Nadolol (80 mg/1) Tablet Oral Monarch Pharmaceuticals, Inc. 2006-10-10 2006-10-10 US Corzide Bendroflumethiazide (5 mg/1) + Nadolol (80 mg/1) Tablet Oral Pfizer Laboratories Div Pfizer Inc 1983-05-25 2019-10-31 US Corzide Bendroflumethiazide (5 mg/1) + Nadolol (80 mg/1) Tablet Oral Physicians Total Care, Inc. 1983-05-25 2010-06-30 US
Categories
- ATC Codes
- C03AB01 — Bendroflumethiazide and potassium
- C03AB — Thiazides and potassium in combination
- C03A — LOW-CEILING DIURETICS, THIAZIDES
- C03 — DIURETICS
- C — CARDIOVASCULAR SYSTEM
- C03EA — Low-ceiling diuretics and potassium-sparing agents
- C03E — DIURETICS AND POTASSIUM-SPARING AGENTS IN COMBINATION
- C03 — DIURETICS
- C — CARDIOVASCULAR SYSTEM
- G01AE — Sulfonamides
- G01A — ANTIINFECTIVES AND ANTISEPTICS, EXCL. COMBINATIONS WITH CORTICOSTEROIDS
- G01 — GYNECOLOGICAL ANTIINFECTIVES AND ANTISEPTICS
- G — GENITO URINARY SYSTEM AND SEX HORMONES
- Drug Categories
- Antihypertensive Agents
- Antihypertensive Agents Indicated for Hypertension
- Benzothiadiazines
- Bradycardia-Causing Agents
- Cardiovascular Agents
- Diuretics
- Genito Urinary System and Sex Hormones
- Gynecological Antiinfectives and Antiseptics
- Heterocyclic Compounds, Fused-Ring
- Hyperglycemia-Associated Agents
- Hypotensive Agents
- Increased Diuresis
- Low-Ceiling Diuretics and Potassium-Sparing Agents
- Membrane Transport Modulators
- Natriuretic Agents
- Sodium Chloride Symporter Inhibitors
- Sulfonamides
- Sulfones
- Sulfur Compounds
- Thiazides
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as 1,2,4-benzothiadiazine-1,1-dioxides. These are aromatic heterocyclic compounds containing a 1,2,4-benzothiadiazine ring system with two S=O bonds at the 1-position.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Thiadiazines
- Sub Class
- Benzothiadiazines
- Direct Parent
- 1,2,4-benzothiadiazine-1,1-dioxides
- Alternative Parents
- Secondary alkylarylamines / Organosulfonamides / Benzene and substituted derivatives / Aminosulfonyl compounds / Azacyclic compounds / Organopnictogen compounds / Organofluorides / Organic oxides / Hydrocarbon derivatives / Alkyl fluorides
- Substituents
- 1,2,4-benzothiadiazine-1,1-dioxide / Alkyl fluoride / Alkyl halide / Amine / Aminosulfonyl compound / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Hydrocarbon derivative / Monocyclic benzene moiety
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- sulfonamide, benzothiadiazine (CHEBI:3013)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 5Q52X6ICJI
- CAS number
- 73-48-3
- InChI Key
- 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-1lambda6,2,4-benzothiadiazine-7-sulfonamide
- SMILES
- NS(=O)(=O)C1=CC2=C(NC(CC3=CC=CC=C3)NS2(=O)=O)C=C1C(F)(F)F
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 References
- FDA Approved Drug Products: CORZIDE (nadolol and bendroflumethiazide) tablets [Link]
- External Links
- Human Metabolome Database
- HMDB0014580
- KEGG Drug
- D00650
- KEGG Compound
- C07758
- PubChem Compound
- 2315
- PubChem Substance
- 46508672
- ChemSpider
- 2225
- BindingDB
- 50238678
- 1369
- ChEBI
- 3013
- ChEMBL
- CHEMBL1684
- Therapeutic Targets Database
- DAP000188
- PharmGKB
- PA448563
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Bendroflumethiazide
- MSDS
- Download (72.8 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Hypertension 1 4 Suspended Prevention Coronavirus Disease 2019 (COVID‑19) / Hypertension 1 1 Completed Not Available Healthy Subjects (HS) 2 1 Recruiting Other Heart Failure 1 Not Available Completed Not Available Coronavirus Disease 2019 (COVID‑19) / COVID / Hypertension 1
Pharmacoeconomics
- Manufacturers
- Apothecon inc div bristol myers squibb
- Packagers
- E.R. Squibb and Sons LLC
- King Pharmaceuticals Inc.
- Physicians Total Care Inc.
- Professional Co.
- Dosage Forms
Form Route Strength Tablet Oral Tablet Oral 5 mg/1 Tablet Oral 5 mg Tablet - Prices
Unit description Cost Unit Bendroflumethiazide powder 45.0USD g Corzide 80-5 tablet 4.29USD tablet Corzide 40-5 mg tablet 3.46USD tablet Corzide 40-5 tablet 3.35USD tablet Corzide 80-5 mg tablet 3.23USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 222-223 °C 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. water solubility 108 mg/L (at 25 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992) logP 1.89 BERTHOD,A ET AL. (1999) logS -3.59 ADME Research, USCD pKa 8.5 SANGSTER (1994) - Predicted Properties
Property Value Source Water Solubility 0.214 mg/mL ALOGPS logP 1.83 ALOGPS logP 1.7 Chemaxon logS -3.3 ALOGPS pKa (Strongest Acidic) 9.04 Chemaxon pKa (Strongest Basic) -3.1 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 118.36 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 93.68 m3·mol-1 Chemaxon Polarizability 36.92 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9643 Blood Brain Barrier - 0.7807 Caco-2 permeable - 0.7105 P-glycoprotein substrate Non-substrate 0.6048 P-glycoprotein inhibitor I Non-inhibitor 0.7889 P-glycoprotein inhibitor II Non-inhibitor 0.8383 Renal organic cation transporter Non-inhibitor 0.8835 CYP450 2C9 substrate Non-substrate 0.708 CYP450 2D6 substrate Non-substrate 0.8398 CYP450 3A4 substrate Non-substrate 0.6596 CYP450 1A2 substrate Inhibitor 0.8745 CYP450 2C9 inhibitor Non-inhibitor 0.907 CYP450 2D6 inhibitor Non-inhibitor 0.9351 CYP450 2C19 inhibitor Non-inhibitor 0.9287 CYP450 3A4 inhibitor Non-inhibitor 0.8607 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9081 Ames test Non AMES toxic 0.8474 Carcinogenicity Non-carcinogens 0.8156 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.0888 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9858 hERG inhibition (predictor II) Non-inhibitor 0.8967
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 199.4121392 predictedDarkChem Lite v0.1.0 [M-H]- 183.27798 predictedDeepCCS 1.0 (2019) [M+H]+ 199.7761392 predictedDarkChem Lite v0.1.0 [M+H]+ 185.636 predictedDeepCCS 1.0 (2019) [M+Na]+ 199.2524392 predictedDarkChem Lite v0.1.0 [M+Na]+ 192.57181 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Transporter activity
- Specific Function
- Key mediator of sodium and chloride reabsorption in this nephron segment, accounting for a significant fraction of renal sodium reabsorption.
- Gene Name
- SLC12A3
- Uniprot ID
- P55017
- Uniprot Name
- Solute carrier family 12 member 3
- Molecular Weight
- 113138.04 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- 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. [Article]
- 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. doi: 10.1152/ajprenal.00528.2007. Epub 2008 Jan 23. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inducer
- General Function
- Voltage-gated potassium channel activity
- Specific Function
- 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 activati...
- Gene Name
- KCNMA1
- Uniprot ID
- Q12791
- Uniprot Name
- Calcium-activated potassium channel subunit alpha-1
- Molecular Weight
- 137558.115 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
- Gene Name
- CA1
- Uniprot ID
- P00915
- Uniprot Name
- Carbonic anhydrase 1
- Molecular Weight
- 28870.0 Da
References
- Tricarico D, Mele A, Conte Camerino D: Carbonic anhydrase inhibitors ameliorate the symptoms of hypokalaemic periodic paralysis in rats by opening the muscular Ca2+-activated-K+ channels. Neuromuscul Disord. 2006 Jan;16(1):39-45. doi: 10.1016/j.nmd.2005.10.005. Epub 2005 Dec 20. [Article]
- Berg JT, Ramanathan S, Gabrielli MG, Swenson ER: Carbonic anhydrase in mammalian vascular smooth muscle. J Histochem Cytochem. 2004 Aug;52(8):1101-6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion in...
- Gene Name
- CA2
- Uniprot ID
- P00918
- Uniprot Name
- Carbonic anhydrase 2
- Molecular Weight
- 29245.895 Da
References
- Tricarico D, Mele A, Conte Camerino D: Carbonic anhydrase inhibitors ameliorate the symptoms of hypokalaemic periodic paralysis in rats by opening the muscular Ca2+-activated-K+ channels. Neuromuscul Disord. 2006 Jan;16(1):39-45. doi: 10.1016/j.nmd.2005.10.005. Epub 2005 Dec 20. [Article]
- Berg JT, Ramanathan S, Gabrielli MG, Swenson ER: Carbonic anhydrase in mammalian vascular smooth muscle. J Histochem Cytochem. 2004 Aug;52(8):1101-6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina an...
- Gene Name
- CA4
- Uniprot ID
- P22748
- Uniprot Name
- Carbonic anhydrase 4
- Molecular Weight
- 35032.075 Da
References
- Tricarico D, Mele A, Conte Camerino D: Carbonic anhydrase inhibitors ameliorate the symptoms of hypokalaemic periodic paralysis in rats by opening the muscular Ca2+-activated-K+ channels. Neuromuscul Disord. 2006 Jan;16(1):39-45. doi: 10.1016/j.nmd.2005.10.005. Epub 2005 Dec 20. [Article]
- Wistrand PJ, Carter ND, Conroy CW, Mahieu I: Carbonic anhydrase IV activity is localized on the exterior surface of human erythrocytes. Acta Physiol Scand. 1999 Feb;165(2):211-8. doi: 10.1046/j.1365-201x.1999.00478.x. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Thiopurine s-methyltransferase activity
- Specific Function
- Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine.
- Gene Name
- TPMT
- Uniprot ID
- P51580
- Uniprot Name
- Thiopurine S-methyltransferase
- Molecular Weight
- 28180.09 Da
References
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at November 03, 2023 23:42