Identification
- Generic Name
- Trichlormethiazide
- DrugBank Accession Number
- DB01021
- Background
A thiazide diuretic with properties similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p830)
- Type
- Small Molecule
- Groups
- Approved, Vet approved
- Structure
Structure for Trichlormethiazide (DB01021)
- Weight
- Average: 380.656
Monoisotopic: 378.90218026 - Chemical Formula
- C8H8Cl3N3O4S2
- Synonyms
- Trichlormethiazide
- triclormetiazida
Pharmacology
- Indication
Used in the treatment of oedema (including that associated with heart failure) and hypertension.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- 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
Trichloromethiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Trichloromethiazide has also been found useful in edema due to various forms of renal dysfunction such as nephrotic syndrome, acute glomer-ulonephritis, and chronic renal failure. Trichloromethiazide is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension. Like other thiazides, Trichloromethiazide 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.
- Mechanism of action
Trichlormethiazide seemingly appears to inhibit the active reabsorption of chloride in the ascending loop of Henle. Additionally, it may also do the same for sodium. These actions subsequently alter electrolyte transfer in the proximal tubule. This results in excretion of sodium, chloride, and water and, hence, diuresis. As a diuretic, Trichloromethiazide 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 Trichloromethiazide 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 Trichloromethiazide 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 ASodium/potassium-transporting ATPase subunit alpha-1 inhibitorHumans UCarbonic anhydrase 1 inhibitorHumans UCarbonic anhydrase 2 inhibitorHumans UCarbonic anhydrase 4 inhibitorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Oral Rat LD50 = 5600 mg/kg, oral Mouse LD50 = 2600 mg/kg
- Pathways
Pathway Category Trichlormethiazide 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 Trichlormethiazide may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy. Abaloparatide Abaloparatide may increase the hypotensive activities of Trichlormethiazide. Abciximab The therapeutic efficacy of Abciximab can be decreased when used in combination with Trichlormethiazide. Acarbose The therapeutic efficacy of Acarbose can be decreased when used in combination with Trichlormethiazide. Acebutolol The therapeutic efficacy of Acebutolol can be increased when used in combination with Trichlormethiazide. - Food Interactions
- Not Available
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
- Anistadin / Carvacron / Diu-Hydrin / Diurese / Fluitran / Kubacron / Metahydrin / Naqua
Categories
- ATC Codes
- G01AE10 — Combinations of sulfonamides
- G01AE — Sulfonamides
- G01A — ANTIINFECTIVES AND ANTISEPTICS, EXCL. COMBINATIONS WITH CORTICOSTEROIDS
- G01 — GYNECOLOGICAL ANTIINFECTIVES AND ANTISEPTICS
- G — GENITO URINARY SYSTEM AND SEX HORMONES
- C03AA — Thiazides, plain
- 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
- Drug Categories
- Antihypertensive Agents
- Benzothiadiazines
- Cardiovascular Agents
- Diuretics
- Genito Urinary System and Sex Hormones
- Gynecological Antiinfectives and Antiseptics
- Heterocyclic Compounds, Fused-Ring
- Hyperglycemia-Associated Agents
- 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 / Benzenoids / Aryl chlorides / Aminosulfonyl compounds / Azacyclic compounds / Organopnictogen compounds / Organochlorides / Organic oxides / Hydrocarbon derivatives show 1 more
- Substituents
- 1,2,4-benzothiadiazine-1,1-dioxide / Alkyl chloride / Alkyl halide / Amine / Aminosulfonyl compound / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid show 15 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- benzothiadiazine (CHEBI:9683)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- Q58C92TUN0
- CAS number
- 133-67-5
- InChI Key
- LMJSLTNSBFUCMU-UHFFFAOYSA-N
- InChI
- InChI=1S/C8H8Cl3N3O4S2/c9-3-1-4-6(2-5(3)19(12,15)16)20(17,18)14-8(13-4)7(10)11/h1-2,7-8,13-14H,(H2,12,15,16)
- IUPAC Name
- 6-chloro-3-(dichloromethyl)-1,1-dioxo-3,4-dihydro-2H-1lambda6,2,4-benzothiadiazine-7-sulfonamide
- SMILES
- NS(=O)(=O)C1=C(Cl)C=C2NC(NS(=O)(=O)C2=C1)C(Cl)Cl
References
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015156
- KEGG Drug
- D00658
- KEGG Compound
- C07767
- PubChem Compound
- 5560
- PubChem Substance
- 46508880
- ChemSpider
- 5359
- BindingDB
- 26998
- 10772
- ChEBI
- 9683
- ChEMBL
- CHEMBL1054
- Therapeutic Targets Database
- DAP000035
- PharmGKB
- PA164752426
- Wikipedia
- Trichlormethiazide
- MSDS
- Download (73.2 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
Pharmacoeconomics
- Manufacturers
- Sanofi aventis us llc
- Schering corp sub schering plough corp
- Lannett co inc
- Mm mast and co
- Impax laboratories inc
- Par pharmaceutical inc
- Sandoz inc
- Tg united labs llc
- Watson laboratories inc
- Packagers
- C.O. Truxton Inc.
- Carlisle Laboratories Inc.
- PD-Rx Pharmaceuticals Inc.
- Professional Co.
- Dosage Forms
Form Route Strength Pill Tablet - Prices
Unit description Cost Unit Trichlormethiazide powder 15.0USD g 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) 270 dec °C PhysProp water solubility 800 mg/L (at 25 °C) MERCK (1989) logP 0.62 SANGSTER (1994) logS -2.68 ADME Research, USCD pKa 8.6 Not Available - Predicted Properties
Property Value Source Water Solubility 0.415 mg/mL ALOGPS logP 0.86 ALOGPS logP 0.97 Chemaxon logS -3 ALOGPS pKa (Strongest Acidic) 8.32 Chemaxon pKa (Strongest Basic) -4.1 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 2 Chemaxon Refractivity 77.44 m3·mol-1 Chemaxon Polarizability 31.97 Å3 Chemaxon Number of Rings 2 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 + 0.9356 Blood Brain Barrier - 0.9431 Caco-2 permeable - 0.7869 P-glycoprotein substrate Non-substrate 0.6958 P-glycoprotein inhibitor I Non-inhibitor 0.8804 P-glycoprotein inhibitor II Non-inhibitor 0.9432 Renal organic cation transporter Non-inhibitor 0.8959 CYP450 2C9 substrate Non-substrate 0.7173 CYP450 2D6 substrate Non-substrate 0.8454 CYP450 3A4 substrate Non-substrate 0.6828 CYP450 1A2 substrate Non-inhibitor 0.9046 CYP450 2C9 inhibitor Non-inhibitor 0.9454 CYP450 2D6 inhibitor Non-inhibitor 0.9582 CYP450 2C19 inhibitor Non-inhibitor 0.9611 CYP450 3A4 inhibitor Non-inhibitor 0.9325 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9502 Ames test Non AMES toxic 0.9209 Carcinogenicity Non-carcinogens 0.844 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 1.8282 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9721 hERG inhibition (predictor II) Non-inhibitor 0.9276
Spectra
- Mass Spec (NIST)
- Download (8.06 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 166.0991319 predictedDarkChem Lite v0.1.0 [M-H]- 164.14183 predictedDeepCCS 1.0 (2019) [M+H]+ 166.6183319 predictedDarkChem Lite v0.1.0 [M+H]+ 166.49982 predictedDeepCCS 1.0 (2019) [M+Na]+ 166.0446319 predictedDarkChem Lite v0.1.0 [M+Na]+ 173.5555 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- 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
- Li J, Wang DH: Function and regulation of epithelial sodium transporters in the kidney of a salt-sensitive hypertensive rat model. J Hypertens. 2007 May;25(5):1065-72. [Article]
- Hasannejad H, Takeda M, Taki K, Shin HJ, Babu E, Jutabha P, Khamdang S, Aleboyeh M, Onozato ML, Tojo A, Enomoto A, Anzai N, Narikawa S, Huang XL, Niwa T, Endou H: Interactions of human organic anion transporters with diuretics. J Pharmacol Exp Ther. 2004 Mar;308(3):1021-9. Epub 2003 Nov 10. [Article]
- Smith SM: Thiazide diuretics. N Engl J Med. 2010 Feb 18;362(7):659-60; author reply 660. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Steroid hormone binding
- Specific Function
- This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates th...
- Gene Name
- ATP1A1
- Uniprot ID
- P05023
- Uniprot Name
- Sodium/potassium-transporting ATPase subunit alpha-1
- Molecular Weight
- 112895.01 Da
References
- Takahashi N, Kondo Y, Fujiwara I, Ito O, Igarashi Y, Abe K: Characterization of Na+ transport across the cell membranes of the ascending thin limb of Henle's loop. Kidney Int. 1995 Mar;47(3):789-94. [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
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- 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. doi: 10.1016/j.bmc.2008.12.023. Epub 2008 Dec 24. [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
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- 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. doi: 10.1016/j.bmc.2008.12.023. Epub 2008 Dec 24. [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
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- 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. doi: 10.1016/j.bmc.2008.12.023. Epub 2008 Dec 24. [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 February 02, 2024 22:47