DT-Web

DB00436 - Bendroflumethiazide


Identification
Name Bendroflumethiazide
Accession Number DB00436 (APRD00666)
Type small molecule
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
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 421.415
Groups approved
Monoisotopic Weight 421.037781946
Pharmacology
Indication For the treatment of high blood pressure and management of edema related to heart failure.
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
Protein binding 96%
Biotransformation Not Available
Route of elimination Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of 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


Solute carrier family 12 member 3
Name Solute carrier family 12 member 3
Gene Name SLC12A3
Pharmacological action yes
Actions inhibitor
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • 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
  • 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
DTHybrid score 0.8501
Calcium-activated potassium channel subunit alpha 1
Name Calcium-activated potassium channel subunit alpha 1
Gene Name KCNMA1
Pharmacological action yes
Actions inducer
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. - Pubmed
DTHybrid score 0.3961
Carbonic anhydrase 1
Name Carbonic anhydrase 1
Gene Name CA1
Pharmacological action unknown
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
DTHybrid score 0.8486
Carbonic anhydrase 2
Name Carbonic anhydrase 2
Gene Name CA2
Pharmacological action unknown
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
DTHybrid score 1.8562
Carbonic anhydrase 4
Name Carbonic anhydrase 4
Gene Name CA4
Pharmacological action unknown
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
DTHybrid score 0.6019

Enzymes


Thiopurine S-methyltransferase
Name Thiopurine S-methyltransferase
Gene Name TPMT
Actions inhibitor
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. - Pubmed
DTHybrid score 0.3991

Predictions


Id Partner name Gene Name Score
3007 Carbonic anhydrase 12 CA12 0.1797
4205 Carbonic anhydrase 9 CA9 0.1796
558 Solute carrier family 12 member 1 SLC12A1 0.1676
1729 Solute carrier family 22 member 6 SLC22A6 0.1328
806 Sodium/potassium-transporting ATPase alpha-1 chain ATP1A1 0.1235
6126 Carbonic anhydrase 7 CA7 0.1194
1253 Interferon gamma IFNG 0.1133
2176 Protein S100-P S100P 0.0971
6123 Carbonic anhydrase 5A, mitochondrial CA5A 0.0655
4512 Cytochrome P450 3A4 CYP3A4 0.061
310 Solute carrier family 12 member 2 SLC12A2 0.0551
253 Sodium/potassium-transporting ATPase gamma chain FXYD2 0.052
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.0499
3426 Glutamine synthetase glnA 0.0486
3987 Glutamine synthetase GLUL 0.0486
87 Hypoxanthine-guanine phosphoribosyltransferase HPRT1 0.0485
4757 Cytochrome P450 2C9 CYP2C9 0.044
6131 Carbonic anhydrase 14 CA14 0.0392
3947 Xanthine dehydrogenase/oxidase XDH 0.0386
6122 Carbonic anhydrase 3 CA3 0.0374
6013 Cytochrome P450 2E1 CYP2E1 0.0363
3932 Glutathione S-transferase A2 GSTA2 0.0291
4031 Glutathione S-transferase A1 GSTA1 0.027
1025 Aquaporin-1 AQP1 0.0263
896 Glutathione S-transferase Mu 1 GSTM1 0.026
2164 Multidrug resistance-associated protein 4 ABCC4 0.0239
6223 Penicillin-binding protein 1C pbpC 0.0227
1198 Serum paraoxonase/arylesterase 1 PON1 0.0227
6142 Solute carrier family 22 member 8 SLC22A8 0.0222
4119 Cytochrome P450 2D6 CYP2D6 0.022
6020 Aldehyde oxidase AOX1 0.0212
3623 Divalent-cation tolerance protein cutA cutA 0.0206
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.02
6016 Cytochrome P450 2C19 CYP2C19 0.0198
241 Calcium-transporting ATPase type 2C member 1 ATP2C1 0.0197
5718 Cytochrome P450 2A6 CYP2A6 0.0196
6171 Solute carrier family 28 member 3 SLC28A3 0.0195
587 Serum albumin ALB 0.0192
537 ATP synthase delta chain, mitochondrial ATP5D 0.0188
158 Sodium channel protein type 1 subunit alpha SCN1A 0.0184
2222 Equilibrative nucleoside transporter 1 SLC29A1 0.0177
559 NADH-ubiquinone oxidoreductase chain 1 MT-ND1 0.0174
1024 Solute carrier family 22 member 11 SLC22A11 0.0174
6024 Cytochrome P450 1A1 CYP1A1 0.0173
6124 Carbonic anhydrase 5B, mitochondrial CA5B 0.0171
482 Glycine receptor subunit alpha-1 GLRA1 0.017
382 Glutamate receptor, ionotropic kainate 1 GRIK1 0.0168
6136 Multidrug resistance-associated protein 5 ABCC5 0.0164
115 Penicillin-binding protein 2 mrdA 0.0138
6069 Penicillin-binding protein 2 mrdA 0.0138
6118 Penicillin-binding protein 2 penA 0.0138
6187 Penicillin-binding protein 2 pbpA 0.0138
6686 Penicillin-binding protein 2 pbp2 0.0138
6939 Penicillin-binding protein 2 mrdA 0.0138
7163 Penicillin-binding protein 2 pbpA 0.0138
705 Glutamate receptor 1 GRIA1 0.0137
3226 UPF0234 protein HI1034 HI_1034 0.0135
3384 Macrophage migration inhibitory factor MIF 0.0132
4200 Cytochrome P450 1A2 CYP1A2 0.013
543 Penicillin-binding protein 1B mrcB 0.0129
6186 Penicillin-binding protein 1B ponB 0.0129
6822 Penicillin-binding protein 1b pbp1b 0.0129
6844 Penicillin-binding protein 1b pbp1b 0.0129
1 Peptidoglycan synthetase ftsI ftsI 0.0129
4155 Peptidoglycan synthetase ftsI ftsI 0.0129
645 Penicillin-binding protein 1A mrcA 0.0127
5805 Penicillin-binding protein 1A ponA 0.0127
6185 Penicillin-binding protein 1A mrcA 0.0127
6799 Penicillin-binding protein 1A pbpA 0.0127
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0124
462 Intermediate conductance calcium-activated potassium channel protein 4 KCNN4 0.0117
3105 M-phase inducer phosphatase 2 CDC25B 0.0108
997 Protein kinase C beta type PRKCB 0.0095
634 Squalene monooxygenase SQLE 0.0088
7196 Squalene monooxygenase ERG1 0.0088
1970 Protein kinase C alpha type PRKCA 0.0087
2408 Tyrosine-protein kinase SYK SYK 0.0086
1768 Guanine nucleotide-binding protein G(I)/G(S)/G(O) gamma-2 subunit GNG2 0.0082
1571 G protein-activated inward rectifier potassium channel 1 KCNJ3 0.0082
1268 Neuropeptide S receptor NPSR1 0.0082
1581 G protein-activated inward rectifier potassium channel 2 KCNJ6 0.0082
6935 Small conductance calcium-activated potassium channel protein 2 KCNN2 0.0077
6933 Calcium-activated potassium channel subunit beta-4 KCNMB4 0.0077
6931 Calcium-activated potassium channel subunit beta-1 KCNMB1 0.0077
6932 Calcium-activated potassium channel subunit beta-3 KCNMB3 0.0077
6934 Small conductance calcium-activated potassium channel protein 1 KCNN1 0.0077
6936 Small conductance calcium-activated potassium channel protein 3 KCNN3 0.0077
6030 Cytochrome P450 2B6 CYP2B6 0.0074
6127 Carbonic anhydrase-related protein CA8 0.0072
6129 Carbonic anhydrase-related protein 11 CA11 0.0072
6133 Sodium channel subunit beta-2 SCN2B 0.0072
6128 Carbonic anhydrase-related protein 10 CA10 0.0072
6132 Sodium channel subunit beta-1 SCN1B 0.0072
6134 Sodium channel subunit beta-3 SCN3B 0.0072
6135 Sodium channel subunit beta-4 SCN4B 0.0072
6072 Potassium channel subfamily K member 3 KCNK3 0.0069
6073 Potassium channel subfamily K member 9 KCNK9 0.0069
3627 UPF0190 protein yedY yedY 0.0067
1392 Catenin beta-1 CTNNB1 0.0067
3352 Structural polyprotein Not Available 0.0067
3628 Structural polyprotein Not Available 0.0067
4892 Structural polyprotein Not Available 0.0067
2236 Casein kinase II subunit alpha CSNK2A1 0.0067
6130 Carbonic anhydrase 13 CA13 0.0067
3803 Sodium channel protein type 3 subunit alpha SCN3A 0.0065
5463 Calcium-activated potassium channel subunit beta 2 KCNMB2 0.0063
215 Sodium channel protein type 11 subunit alpha SCN11A 0.0061
6263 cAMP-dependent protein kinase catalytic subunit alpha PRKACA 0.0059
3802 Sodium channel protein type 2 subunit alpha SCN2A 0.0057
591 Glutamate [NMDA] receptor subunit 3B GRIN3B 0.0055
3804 Sodium channel protein type 4 subunit alpha SCN4A 0.0053
1995 Sodium channel protein type 9 subunit alpha SCN9A 0.0053
514 Potassium voltage-gated channel subfamily H member 6 KCNH6 0.0052
772 Potassium voltage-gated channel subfamily H member 7 KCNH7 0.0052
837 Glutamate [NMDA] receptor subunit epsilon-1 GRIN2A 0.0051
15 Voltage-dependent T-type calcium channel subunit alpha-1I CACNA1I 0.0048
2207 Rhodopsin RHO 0.0047
365 Dihydrofolate reductase DHFR 0.0046
2381 Dihydrofolate reductase DFR1 0.0046
2833 Dihydrofolate reductase Not Available 0.0046
2931 Dihydrofolate reductase folA 0.0046
3544 Dihydrofolate reductase folA 0.0046
3682 Dihydrofolate reductase folA 0.0046
6642 Dihydrofolate reductase folA 0.0046
6756 Dihydrofolate reductase dfrA 0.0046
535 Voltage-dependent T-type calcium channel subunit alpha-1G CACNA1G 0.0046
260 Cytochrome P450 51 ERG11 0.0045
761 Cytochrome P450 51 ERG11 0.0045
3163 Cytochrome P450 51 cyp51 0.0045
6046 Voltage-gated calcium channel beta 1 subunit splice variant CavB1d CACNB1 0.0044
964 Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H 0.0044
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0043
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0042
315 Arginase-1 ARG1 0.004
6045 Voltage-dependent calcium channel subunit alpha-2/delta-3 CACNA2D3 0.004
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0039
1588 Multidrug resistance protein 1 ABCB1 0.0037
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0035
3939 Amine oxidase [flavin-containing] B MAOB 0.0035
3941 Amine oxidase [flavin-containing] A MAOA 0.0035
7 Nitric oxide synthase, inducible NOS2 0.0035
3811 Cytochrome P450 19A1 CYP19A1 0.0034
291 Nitric-oxide synthase, endothelial NOS3 0.0034
3970 Voltage-dependent N-type calcium channel subunit alpha-1B CACNA1B 0.0031
762 Voltage-dependent calcium channel subunit alpha-2/delta-1 CACNA2D1 0.0026
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0026
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0026
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0026
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0025
6040 6-phosphogluconate dehydrogenase, decarboxylating PGD 0.002
6152 Solute carrier organic anion transporter family member 2A1 SLCO2A1 0.002
6107 Cytochrome P450 3A7 CYP3A7 0.0016
4118 Cytochrome P450 3A5 CYP3A5 0.0016
4924 Cytochrome P450 2C8 CYP2C8 0.0015
118 Organic cation/carnitine transporter 2 SLC22A5 0.0013
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0012
4037 Hypothetical protein GPX1 0.0008
4297 Hypothetical protein SP_1951 0.0008
4521 Hypothetical protein BC_2969 0.0008
4540 Hypothetical protein TM_1070 0.0008
4555 Hypothetical protein MT1739 0.0008
4569 Hypothetical protein mshD 0.0008
4578 Hypothetical protein PA3270 0.0008
4747 Hypothetical protein PA3967 0.0008
5177 Hypothetical protein TM_0096 0.0008
5194 Hypothetical protein PA1204 0.0008
5240 Hypothetical protein Rv2991 0.0008
5370 Hypothetical protein TM_1158 0.0008
5710 Hypothetical protein Tb927.5.1360 0.0008
4527 Putative hydrolase ycdX ycdX 0.0008
4536 Transcriptional regulator, IclR family TM_0065 0.0008
2501 Protein ygbM ygbM 0.0008
4545 Molybdopterin-converting factor subunit 2 moaE 0.0008
4522 Arginine N-succinyltransferase subunit alpha astA 0.0008
4106 Guanylate kinase GUK1 0.0008
4516 Guanylate kinase gmk 0.0008
4538 Hypothetical protein VC1899 VC_1899 0.0008
4529 Oxalate decarboxylase oxdC oxdC 0.0008
4514 Citrate lyase beta subunit-like protein citE 0.0008
4781 Citrate lyase beta subunit-like protein DR_1240 0.0008
4526 Oligopeptide ABC transporter, periplasmic oligopeptide-binding protein TM_1223 0.0008
4524 Mannose-6-phosphate isomerase yvyI 0.0008
4535 Glutaconyl-CoA decarboxylase subunit alpha gcdA 0.0008
4547 Iron binding protein FbpA fbpA 0.0008
4548 Gyrase B gyrB 0.0008
4546 Aminotransferase, putative TM_1131 0.0008
658 Para-aminobenzoate synthase component 1 pabB 0.0008
4515 Peripheral plasma membrane protein CASK CASK 0.0008
4496 C-terminal-binding protein 1 CTBP1 0.0008
4517 Probable butyrate kinase 2 buk2 0.0007
3261 Signal recognition particle protein ffh 0.0007
4528 Phenazine biosynthesis protein PhzD phzD1 0.0007
4533 Glyoxalase family protein BC_1747 0.0007
56 Delta-aminolevulinic acid dehydratase ALAD 0.0007
2356 Delta-aminolevulinic acid dehydratase hemB 0.0007
3613 Delta-aminolevulinic acid dehydratase hemB 0.0007
3674 Delta-aminolevulinic acid dehydratase hemB 0.0007
3759 Glutathione S-transferase gst 0.0007
4541 Glutathione S-transferase GST 0.0007
4542 Glutaminase 1 glsA1 0.0007
4544 Glutaminase 1 glsA1 0.0007
2929 (S)-2-haloacid dehalogenase dhlB 0.0007
2995 (S)-2-haloacid dehalogenase Not Available 0.0007
3237 Beta-lactamase OXA-2 bla 0.0007
4532 Gephyrin GPHN 0.0007
2230 Catalase CAT 0.0007
3249 Catalase katA 0.0007
3625 Catalase katA 0.0007
4539 Catalase katA 0.0007
4941 Catalase katB 0.0007
4531 Putative ketoacyl reductase actIII 0.0007
2775 Dihydroorotate dehydrogenase pyrD 0.0007
3467 Methylglyoxal synthase mgsA 0.0007
3583 6-phosphogluconolactonase pgl 0.0007
2525 3-phosphoshikimate 1-carboxyvinyltransferase aroA 0.0006
3201 3-phosphoshikimate 1-carboxyvinyltransferase aroA 0.0006
2688 Peptide deformylase def 0.0006
2708 Peptide deformylase def 0.0006
3004 Peptide deformylase def 0.0006
4337 Peptide deformylase def 0.0006
4338 Peptide deformylase def 0.0006
5368 Peptide deformylase def 0.0006
5371 Peptide deformylase def 0.0006
6375 Peptide deformylase def 0.0006
6378 Peptide deformylase def 0.0006
6379 Peptide deformylase def 0.0006
6776 Peptide deformylase def 0.0006
6900 Peptide deformylase def 0.0006
4534 Cytohesin-2 CYTH2 0.0006
2548 Subtilisin Carlsberg apr 0.0006
4269 Hypoxanthine-guanine phosphoribosyltransferase, putative HGPRTase 0.0006
760 Fibroblast growth factor 1 FGF1 0.0005
810 Heme oxygenase 1 HMOX1 0.0005
3391 Heme oxygenase 1 pbsA1 0.0005
3027 Streptavidin Not Available 0.0005
500 Monocarboxylate transporter 4 SLC16A3 0.0005
76 Nitric-oxide synthase, brain NOS1 0.0004
5682 Ribonuclease pancreatic RNASE1 0.0004
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