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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyChlorothiazide
Identification
- Name
- Chlorothiazide
- Accession Number
- DB00880 (APRD00721)
- Type
- Small Molecule
- Groups
- Approved, Vet approved
- Description
A thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p812)
- Structure
Structure for Chlorothiazide (DB00880)
- Synonyms
- 6-Chloro-1,1-dioxo-1,2-dihydro-1lambda*6*-benzo[1,2,4]thiadiazine-7-sulfonic acid amide
- 6-chloro-7-sulfamoyl-2H-1,2,4-benzothiadiazine 1,1-dioxide
- Chlorothiazid
- Chlorothiazide
- Chlorothiazidum
- Chlorthiazide
- Clorotiazida
- Product Ingredients
Ingredient UNII CAS InChI Key Chlorothiazide sodium SN86FG7N2K 7085-44-1 CPIWHAFLBZQYLQ-UHFFFAOYSA-N - Product Images
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Diuril Suspension 250 mg/5mL Oral Merck Sharp & Dohme Limited 1961-10-06 2008-10-31 US 
Diuril Suspension 250 mg/5mL Oral Salix Pharmaceuticals 1962-02-15 Not applicable US DIURIL Sodium Injection, powder, lyophilized, for solution 0.5 g/18mL Intravenous MERCK and CO., INC. 2006-04-07 2006-08-21 US Sodium Diuril Injection, powder, lyophilized, for solution 0.5 g/18mL Intravenous Lundbeck Inc. 1958-10-03 2011-12-22 US Sodium Diuril Injection 0.5 mg/18mL Intravenous Oak Pharmaceuticals, Inc. (Subsidiary of Akorn, Inc.) 1958-10-03 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Chlorothiazide Tablet 250 mg/1 Oral Golden State Medical Supply 2005-08-30 2017-01-02 US Chlorothiazide Tablet 250 mg/1 Oral Mylan Pharmaceuticals Inc. 1975-06-26 Not applicable US Chlorothiazide Tablet 500 mg/1 Oral Physicians Total Care, Inc. 2005-08-30 2012-06-30 US Chlorothiazide Injection, powder, lyophilized, for solution 500 mg/18mL Intravenous Fresenius Kabi 2009-10-21 Not applicable US Chlorothiazide Tablet 500 mg/1 Oral West Ward Pharmaceutical 2005-08-30 Not applicable US 
Chlorothiazide Tablet 250 mg/1 Oral West Ward Pharmaceutical 2005-08-30 Not applicable US Chlorothiazide Tablet 250 mg/1 Oral Avera McKennan Hospital 2015-03-01 2018-05-21 US Chlorothiazide Tablet 500 mg/1 Oral Golden State Medical Supply 2005-08-30 2017-01-02 US 
Chlorothiazide Tablet 500 mg/1 Oral Mylan Pharmaceuticals Inc. 1975-07-17 Not applicable US 
Chlorothiazide Sodium Injection, powder, lyophilized, for solution 500 mg/18mL Intravenous AMERICAN REGENT, INC. 2015-04-01 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Diupres Chlorothiazide (250 mg/1) + Reserpine (0.125 mg/1) Tablet Oral Merck & Co., Inc. 2006-03-02 2006-07-13 US Diupres Chlorothiazide (500 mg/1) + Reserpine (0.125 mg/1) Tablet Oral Merck & Co., Inc. 2006-03-02 2006-07-13 US Supres 150 Tab Chlorothiazide (150 mg) + Methyldopa (250 mg) Tablet Oral Merck Frosst Canada & Cie, Merck Frosst Canada & Co. 1972-12-31 2000-06-14 Canada 
Supres 250 Tab Chlorothiazide (250 mg) + Methyldopa (250 mg) Tablet Oral Merck Frosst Canada & Cie, Merck Frosst Canada & Co. 1972-12-31 2000-06-14 Canada - Categories
- Amides
- Antihypertensive Agents
- Benzothiadiazines
- Cardiovascular Agents
- Diuretics
- Genito Urinary System and Sex Hormones
- Gynecological Antiinfectives and Antiseptics
- Hyperglycemia-Associated Agents
- Hypotensive Agents
- Increased Diuresis
- Membrane Transport Modulators
- Natriuretic Agents
- OAT1/SLC22A6 inhibitors
- Sodium Chloride Symporter Inhibitors
- Sulfonamides
- Sulfones
- Sulfur Compounds
- Thiazides
- UNII
- 77W477J15H
- CAS number
- 58-94-6
- Weight
- Average: 295.723
Monoisotopic: 294.948824782 - Chemical Formula
- C7H6ClN3O4S2
- InChI Key
- JBMKAUGHUNFTOL-UHFFFAOYSA-N
- InChI
- InChI=1S/C7H6ClN3O4S2/c8-4-1-5-7(2-6(4)16(9,12)13)17(14,15)11-3-10-5/h1-3H,(H,10,11)(H2,9,12,13)
- IUPAC Name
- 6-chloro-1,1-dioxo-4H-1λ⁶,2,4-benzothiadiazine-7-sulfonamide
- SMILES
- NS(=O)(=O)C1=C(Cl)C=C2NC=NS(=O)(=O)C2=C1
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Pharmacology
- Indication
Chlorothiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. It 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.
- Associated Conditions
- Pharmacodynamics
Like other thiazides, chlorothiazide promotes water loss from the body (diuretics). 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. Chlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic efficacy. Chlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate. After oral doses, 10-15 percent of the dose is excreted unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.
- Mechanism of action
As a diuretic, chlorothiazide 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 chlorothiazide 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 chlorothiazide 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 ACarbonic anhydrase 1 inhibitorHumans ACarbonic anhydrase 2 inhibitorHumans - Absorption
Rapidly absorbed following oral administration.
- Volume of distribution
- Not Available
- Protein binding
Approximately 40% bound to plasma proteins.
- Metabolism
Chlorothiazide is not metabolized but is eliminated rapidly by the kidney.
- Route of elimination
Chlorothiazide is not metabolized but is eliminated rapidly by the kidney. After oral doses, 10 to 15 percent of the dose is excreted unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.
- Half life
45-120 minutes
- Clearance
- Not Available
- Toxicity
Oral, rat LD50: > 10 g/kg. Signs of overdose include those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered hypokalemia may accentuate cardiac arrhythmias.
- Affected organisms
- Humans and other mammals
- Pathways
Pathway Category Chlorothiazide Action Pathway Drug action - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid The risk or severity of hypotension can be increased when Chlorothiazide is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid. 1-benzylimidazole 1-benzylimidazole may decrease the antihypertensive activities of Chlorothiazide. 1alpha-Hydroxyvitamin D5 The risk or severity of hypercalcemia can be increased when Chlorothiazide is combined with 1alpha-Hydroxyvitamin D5. 2,4-thiazolidinedione The therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Chlorothiazide. 2,5-Dimethoxy-4-ethylamphetamine 2,5-Dimethoxy-4-ethylamphetamine may decrease the antihypertensive activities of Chlorothiazide. 2,5-Dimethoxy-4-ethylthioamphetamine 2,5-Dimethoxy-4-ethylthioamphetamine may decrease the antihypertensive activities of Chlorothiazide. 4-Bromo-2,5-dimethoxyamphetamine 4-Bromo-2,5-dimethoxyamphetamine may decrease the antihypertensive activities of Chlorothiazide. 4-Methoxyamphetamine 4-Methoxyamphetamine may decrease the antihypertensive activities of Chlorothiazide. 5-methoxy-N,N-dimethyltryptamine 5-methoxy-N,N-dimethyltryptamine may decrease the antihypertensive activities of Chlorothiazide. 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypotensive activities of Chlorothiazide. - Food Interactions
- Not Available
References
- Synthesis Reference
Eugene S. Barabas, "Water soluble complex of a poly (vinyl lactam) and chlorothiazide and process for producing same." U.S. Patent US4713238, issued December, 1985.
US4713238- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015018
- KEGG Drug
- D00519
- KEGG Compound
- C07461
- PubChem Compound
- 2720
- PubChem Substance
- 46507032
- ChemSpider
- 2619
- BindingDB
- 39351
- ChEBI
- 3640
- ChEMBL
- CHEMBL842
- Therapeutic Targets Database
- DAP000605
- PharmGKB
- PA448953
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Chlorothiazide
- ATC Codes
- C03AB04 — Chlorothiazide and potassium
- C03AB — Thiazides and potassium in combination
- C03A — LOW-CEILING DIURETICS, THIAZIDES
- 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
- C03AA — Thiazides, plain
- C03A — LOW-CEILING DIURETICS, THIAZIDES
- C03 — DIURETICS
- C — CARDIOVASCULAR SYSTEM
- MSDS
- Download (72.7 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Prevention Cardiovascular Disease (CVD) / Heart Diseases / High Blood Pressure (Hypertension) / Vascular Diseases 1 4 Completed Treatment Heart Failure 1 4 Enrolling by Invitation Treatment Acute Heart Failure (AHF) / Cardiovascular Disease (CVD) / Heart Failure / Heart Failure With Reduced Ejection Fraction (HFrEF) 1 Not Available Completed Screening Diabetes Insipidus, Nephrogenic 1 Not Available Recruiting Diagnostic Heart Failure 1
Pharmacoeconomics
- Manufacturers
- Salix pharmaceuticals inc
- Abc holding corp
- Lederle laboratories div american cyanamid co
- Mylan pharmaceuticals inc
- Sandoz inc
- Watson laboratories inc
- West ward pharmaceutical corp
- Lundbeck inc
- App pharmaceuticals llc
- Packagers
- APP Pharmaceuticals
- Ben Venue Laboratories Inc.
- Endo Pharmaceuticals Inc.
- Lundbeck Inc.
- Major Pharmaceuticals
- Merck & Co.
- Murfreesboro Pharmaceutical Nursing Supply
- Mylan
- PD-Rx Pharmaceuticals Inc.
- Physicians Total Care Inc.
- Salix Pharmaceuticals
- Sandhills Packaging Inc.
- UDL Laboratories
- Watson Pharmaceuticals
- West-Ward Pharmaceuticals
- Dosage forms
Form Route Strength Tablet Oral 250 mg/1 Tablet Oral 500 mg/1 Injection Intravenous 500 mg/1 Injection, powder, lyophilized, for solution Intravenous 500 mg/18mL Suspension Oral 250 mg/5mL Injection, powder, lyophilized, for solution Intravenous 0.5 g/18mL Injection Intravenous 0.5 mg/18mL Tablet Oral - Prices
Unit description Cost Unit Diuril sodium 500 mg vial 519.62USD vial Chlorothiazide sod 500 mg vial 357.24USD vial Microzide 12.5 mg capsule 0.95USD capsule Aldoclor 250-250 mg tablet 0.67USD tablet Chlorothiazide 500 mg tablet 0.36USD tablet Chlorothiazide 250 mg tablet 0.28USD 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) 342.5-343 Novello, F.C.; US. Patent 2,809,194; October 8,1957; assigned to Merck & Co.,Inc. Hinkley, D.F.; US. Patent 2,937,169; May 17,1960; assigned to Merck & Co., Inc. water solubility 266 mg/L (at 30 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992) logP -0.24 HANSCH,C ET AL. (1995) logS -3.05 ADME Research, USCD Caco2 permeability -6.72 ADME Research, USCD pKa 6.85 MERCK INDEX (1996) - Predicted Properties
Property Value Source Water Solubility 0.398 mg/mL ALOGPS logP 0.41 ALOGPS logP -0.44 ChemAxon logS -2.9 ALOGPS pKa (Strongest Acidic) 9.1 ChemAxon pKa (Strongest Basic) 1.15 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 6 ChemAxon Hydrogen Donor Count 2 ChemAxon Polar Surface Area 118.69 Å2 ChemAxon Rotatable Bond Count 1 ChemAxon Refractivity 62.51 m3·mol-1 ChemAxon Polarizability 24.55 Å3 ChemAxon Number of Rings 2 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 0.9119 Blood Brain Barrier - 0.9506 Caco-2 permeable - 0.7368 P-glycoprotein substrate Non-substrate 0.706 P-glycoprotein inhibitor I Non-inhibitor 0.8482 P-glycoprotein inhibitor II Non-inhibitor 0.8381 Renal organic cation transporter Non-inhibitor 0.8177 CYP450 2C9 substrate Non-substrate 0.755 CYP450 2D6 substrate Non-substrate 0.8379 CYP450 3A4 substrate Non-substrate 0.6308 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.923 CYP450 2C19 inhibitor Non-inhibitor 0.9382 CYP450 3A4 inhibitor Non-inhibitor 0.8901 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8658 Ames test Non AMES toxic 0.9132 Carcinogenicity Non-carcinogens 0.7792 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 1.5023 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9654 hERG inhibition (predictor II) Non-inhibitor 0.9352
Spectra
- Mass Spec (NIST)
- Download (10.1 KB)
- Spectra
Taxonomy
- 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
- Organosulfonamides / Benzenoids / Aryl chlorides / Aminosulfonyl compounds / Propargyl-type 1,3-dipolar organic compounds / Formamidines / Azacyclic compounds / Organopnictogen compounds / Organochlorides / Organic oxides show 1 more
- Substituents
- 1,2,4-benzothiadiazine-1,1-dioxide / Aryl chloride / Aryl halide / Organosulfonic acid amide / Benzenoid / Organic sulfonic acid or derivatives / Organosulfonic acid or derivatives / Sulfonyl / Aminosulfonyl compound / Propargyl-type 1,3-dipolar organic compound show 14 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- benzothiadiazine (CHEBI:3640)
Targets
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- 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
- Puscas I, Coltau M, Baican M, Domuta G, Hecht A: Vasodilatory effect of diuretics is dependent on inhibition of vascular smooth muscle carbonic anhydrase by a direct mechanism of action. Drugs Exp Clin Res. 1999;25(6):271-9. [PubMed:10713865]
- Puscas I, Coltau M, Baican M, Pasca R, Domuta G: The inhibitory effect of diuretics on carbonic anhydrases. Res Commun Mol Pathol Pharmacol. 1999;105(3):213-36. [PubMed:10954127]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- 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
- Weiner ID, Verlander JW: Renal and hepatic expression of the ammonium transporter proteins, Rh B Glycoprotein and Rh C Glycoprotein. Acta Physiol Scand. 2003 Dec;179(4):331-8. [PubMed:14656370]
- Puscas I, Coltau M, Baican M, Pasca R, Domuta G: The inhibitory effect of diuretics on carbonic anhydrases. Res Commun Mol Pathol Pharmacol. 1999;105(3):213-36. [PubMed:10954127]
- Verlander JW, Miller RT, Frank AE, Royaux IE, Kim YH, Weiner ID: Localization of the ammonium transporter proteins RhBG and RhCG in mouse kidney. Am J Physiol Renal Physiol. 2003 Feb;284(2):F323-37. Epub 2002 Oct 8. [PubMed:12388412]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
References
- Uwai Y, Saito H, Hashimoto Y, Inui KI: Interaction and transport of thiazide diuretics, loop diuretics, and acetazolamide via rat renal organic anion transporter rOAT1. J Pharmacol Exp Ther. 2000 Oct;295(1):261-5. [PubMed:10991988]
Drug created on June 13, 2005 07:24 / Updated on December 14, 2018 05:49