DT-Web

DB00562 - Benzthiazide


Identification
Name Benzthiazide
Accession Number DB00562 (APRD00728)
Type small molecule
Description Benzthiazide is used to treat hypertension and edema. Like other thiazides, benzthiazide promotes water loss from the body (diuretics). They inhibit 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.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 431.937
Groups approved
Monoisotopic Weight 430.983495728
Pharmacology
Indication For the treatment of high blood pressure and management of edema.
Mechanism of action As a diuretic, benzthiazide 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 benzthiazide 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 benzthiazide 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 in the digestive tract.
Protein binding 30%
Biotransformation Not Available
Route of elimination Not Available
Toxicity Symptoms of overdose include nausea, vomiting, fatigue, urinary problems and drowsiness.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Digoxin Possible electrolyte variations and arrhythmias
Lithium The thiazide diuretic, benzthiazide, may increase serum levels of lithium.
Food Interactions Not Available

Targets


Solute carrier family 12 member 3
Name Solute carrier family 12 member 3
Gene Name SLC12A3
Pharmacological action yes
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 0.8945
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 0.9206
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
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 1.916
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 0.6943
Carbonic anhydrase 9
Name Carbonic anhydrase 9
Gene Name CA9
Pharmacological action unknown
Actions inhibitor
References
  • Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009 Feb 1;17(3):1214-21. Epub 2008 Dec 24. - Pubmed
DTHybrid score 0.4299
Carbonic anhydrase 12
Name Carbonic anhydrase 12
Gene Name CA12
Pharmacological action unknown
Actions inhibitor
References
  • Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009 Feb 1;17(3):1214-21. Epub 2008 Dec 24. - Pubmed
DTHybrid score 0.43

Predictions


Id Partner name Gene Name Score
610 Calcium-activated potassium channel subunit alpha 1 KCNMA1 0.2436
558 Solute carrier family 12 member 1 SLC12A1 0.1756
1729 Solute carrier family 22 member 6 SLC22A6 0.157
6126 Carbonic anhydrase 7 CA7 0.156
806 Sodium/potassium-transporting ATPase alpha-1 chain ATP1A1 0.1134
6123 Carbonic anhydrase 5A, mitochondrial CA5A 0.1056
6131 Carbonic anhydrase 14 CA14 0.0834
1405 Thiopurine S-methyltransferase TPMT 0.0804
6122 Carbonic anhydrase 3 CA3 0.0795
6124 Carbonic anhydrase 5B, mitochondrial CA5B 0.0649
310 Solute carrier family 12 member 2 SLC12A2 0.0551
4512 Cytochrome P450 3A4 CYP3A4 0.0545
253 Sodium/potassium-transporting ATPase gamma chain FXYD2 0.052
4757 Cytochrome P450 2C9 CYP2C9 0.0391
997 Protein kinase C beta type PRKCB 0.035
634 Squalene monooxygenase SQLE 0.0327
7196 Squalene monooxygenase ERG1 0.0327
1970 Protein kinase C alpha type PRKCA 0.032
2408 Tyrosine-protein kinase SYK SYK 0.0318
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.0317
158 Sodium channel protein type 1 subunit alpha SCN1A 0.0311
3426 Glutamine synthetase glnA 0.0308
3987 Glutamine synthetase GLUL 0.0308
6127 Carbonic anhydrase-related protein CA8 0.0282
6129 Carbonic anhydrase-related protein 11 CA11 0.0281
6128 Carbonic anhydrase-related protein 10 CA10 0.0281
6133 Sodium channel subunit beta-2 SCN2B 0.0281
6132 Sodium channel subunit beta-1 SCN1B 0.0281
6134 Sodium channel subunit beta-3 SCN3B 0.0281
6135 Sodium channel subunit beta-4 SCN4B 0.0281
1025 Aquaporin-1 AQP1 0.0263
6130 Carbonic anhydrase 13 CA13 0.025
6013 Cytochrome P450 2E1 CYP2E1 0.0249
2236 Casein kinase II subunit alpha CSNK2A1 0.0247
3803 Sodium channel protein type 3 subunit alpha SCN3A 0.0246
6016 Cytochrome P450 2C19 CYP2C19 0.0237
215 Sodium channel protein type 11 subunit alpha SCN11A 0.0232
1024 Solute carrier family 22 member 11 SLC22A11 0.0218
6263 cAMP-dependent protein kinase catalytic subunit alpha PRKACA 0.0217
3802 Sodium channel protein type 2 subunit alpha SCN2A 0.0217
3623 Divalent-cation tolerance protein cutA cutA 0.0206
3804 Sodium channel protein type 4 subunit alpha SCN4A 0.02
1995 Sodium channel protein type 9 subunit alpha SCN9A 0.0198
6024 Cytochrome P450 1A1 CYP1A1 0.0189
15 Voltage-dependent T-type calcium channel subunit alpha-1I CACNA1I 0.0179
535 Voltage-dependent T-type calcium channel subunit alpha-1G CACNA1G 0.017
382 Glutamate receptor, ionotropic kainate 1 GRIK1 0.0168
964 Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H 0.0162
6020 Aldehyde oxidase AOX1 0.015
3226 UPF0234 protein HI1034 HI_1034 0.0135
3384 Macrophage migration inhibitory factor MIF 0.0132
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0131
3939 Amine oxidase [flavin-containing] B MAOB 0.0131
3941 Amine oxidase [flavin-containing] A MAOA 0.013
3105 M-phase inducer phosphatase 2 CDC25B 0.0108
4119 Cytochrome P450 2D6 CYP2D6 0.0087
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0086
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
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
6046 Voltage-gated calcium channel beta 1 subunit splice variant CavB1d CACNB1 0.0044
315 Arginase-1 ARG1 0.004
6045 Voltage-dependent calcium channel subunit alpha-2/delta-3 CACNA2D3 0.004
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
5718 Cytochrome P450 2A6 CYP2A6 0.0018
6030 Cytochrome P450 2B6 CYP2B6 0.0017
6107 Cytochrome P450 3A7 CYP3A7 0.0016
4118 Cytochrome P450 3A5 CYP3A5 0.0016
4924 Cytochrome P450 2C8 CYP2C8 0.0015
4200 Cytochrome P450 1A2 CYP1A2 0.0015
1588 Multidrug resistance protein 1 ABCB1 0.0014
118 Organic cation/carnitine transporter 2 SLC22A5 0.0013
6142 Solute carrier family 22 member 8 SLC22A8 0.0013
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0012
587 Serum albumin ALB 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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