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Details

Stereochemistry ACHIRAL
Molecular Formula C7H6ClN3O4S2
Molecular Weight 295.7256
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CHLOROTHIAZIDE

SMILES

c1c(c(cc2c1N=CNS2(=O)=O)S(=O)(=O)N)Cl

InChI

InChIKey=JBMKAUGHUNFTOL-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Description
Curator's Comment:: https://www.drugs.com/pro/diuril-injection.html

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. 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. It is marketed under the brand name Diuril.

Originator

Curator's Comment:: Chlorothiazide was synthesized by Novello and Sprague in 1957

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Diuril

Approved Use

Intravenous Sodium DIURIL is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Intravenous Sodium DIURIL has also been found useful in edema due to various forms of renal dysfunction such as nephrotic syndrome, acute glomerulonephritis, and chronic renal failure.

Launch Date

-355017600000
Primary
Diuril

Approved Use

Intravenous Sodium DIURIL is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Intravenous Sodium DIURIL has also been found useful in edema due to various forms of renal dysfunction such as nephrotic syndrome, acute glomerulonephritis, and chronic renal failure.

Launch Date

-355017600000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
682.97 ng/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CHLOROTHIAZIDE plasma
Sus scrofa
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
806.27 ng × h/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CHLOROTHIAZIDE plasma
Sus scrofa
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
0.7 h
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CHLOROTHIAZIDE plasma
Sus scrofa
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
1000 mg 2 times / day multiple, oral
Recommended
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources:
unhealthy
Disc. AE: Hypersensitivity, Azotemia...
AEs leading to
discontinuation/dose reduction:
Hypersensitivity
Azotemia
Systemic lupus erythematosus reactivation
Sources:
AEs

AEs

AESignificanceDosePopulation
Azotemia Disc. AE
1000 mg 2 times / day multiple, oral
Recommended
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources:
unhealthy
Hypersensitivity Disc. AE
1000 mg 2 times / day multiple, oral
Recommended
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources:
unhealthy
Systemic lupus erythematosus reactivation Disc. AE
1000 mg 2 times / day multiple, oral
Recommended
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources:
unhealthy
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Drug as perpetrator​Drug as victim
PubMed

PubMed

TitleDatePubMed
Toxic effects of a chlorothiazide-diazoxide combination on adipose tissue and kidneys of intact rats.
1968 Jun
Metabolic and hormonal studies in a patient with primary aldosteronism, presenting with acute hypokalaemic paresis induced by chlorothiazide.
1968 May
Iliacus haematoma syndrome as a complication of anticoagulant therapy.
1968 Oct 12
On the mechanism of lithium-induced diabetes insipidus in man and the rat.
1974 Apr
Cimetidine and visual hallucinations.
1978 Jul 21
Renal calcifications: a complication of long-term furosemide therapy in preterm infants.
1982 Sep
Reversal of vitamin-D2-induced hypercalciuria by chlorothiazide.
1983 Feb
Thiazide-induced hyponatremia.
1983 Nov
Diuretic-associated pancreatitis: a collective review and illustrative cases.
1987 Sep
Thiazide therapy for ACTH-induced hypercalciuria and nephrolithiasis.
1992 Mar
Are certain diuretics also anticonvulsants?
2001 Oct
Electrochemical behavior of the antituberculosis drug isoniazid and its square-wave adsorptive stripping voltammetric estimation in bulk form, tablets and biological fluids at a mercury electrode.
2003 Nov 24
Hyperinsulinism in tyrosinaemia type I.
2005
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Thiazide diuretics and the risk of gallbladder disease requiring surgery in women.
2005 Mar 14
Releasing the flood waters: diuril and the reshaping of hypertension.
2005 Winter
Fast gas chromatographic/mass spectrometric determination of diuretics and masking agents in human urine: Development and validation of a productive screening protocol for antidoping analysis.
2006 Dec 1
Healing virtue: Saludadores versus witches in early modern Spain.
2009
Expression of therapeutic misconception amongst Egyptians: a qualitative pilot study.
2009 Jun 30
Do new drugs increase life expectancy? A critique of a Manhattan Institute paper.
2009 May
Impacts of intensive agricultural irrigation and livestock farming on a semi-arid Mediterranean catchment.
2010 Aug
Transparotid approach for mandibular condylar neck and subcondylar fractures.
2010 Dec
Running away experience and psychoactive substance use among adolescents in Taiwan: multi-city street outreach survey.
2010 Jan 20
Thiazide-induced hyponatremia.
2010 Jun
Speeding up the process urine sample pre-treatment: some perspectives on the use of microwave assisted extraction in the anti-doping field.
2010 Jun 15
Hypertension, antihypertensive medication use, and breast cancer risk in the California Teachers Study cohort.
2010 Oct
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.
2015 May 18
Patents

Sample Use Guides

The usual adult dosage is 0.5 to 1 g once or twice a day.
Route of Administration: Intravenous
In Vitro Use Guide
Chlorothiazide (1000 uM) inhibited osteocalcin secretion (-42 +/- 12.7%) in human model cell line MG-63
Name Type Language
CHLOROTHIAZIDE
EP   GREEN BOOK   HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD  
INN  
Official Name English
CHLOROTHIAZIDE [ORANGE BOOK]
Common Name English
CHLOROTHIAZIDE [VANDF]
Common Name English
CHLOROTHIAZIDE [JAN]
Common Name English
6-CHLORO-2H-1,2,4-BENZOTHIADIAZINE-7-SULFONAMIDE 1,1-DIOXIDE
Systematic Name English
CHLOROTHIAZIDE [EP]
Common Name English
CHLOROTHIAZIDE [GREEN BOOK]
Common Name English
DIURIL
Brand Name English
CHLOROTHIAZIDE [WHO-DD]
Common Name English
CHLOROTHIAZIDE [HSDB]
Common Name English
NSC-25693
Code English
2H-1,2,4-BENZOTHIADIAZINE-7-SULFONAMIDE, 6-CHLORO-, 1,1-DIOXIDE
Systematic Name English
CHLOROTHIAZIDE [INN]
Common Name English
CHLOROTHIAZIDE [USP MONOGRAPH]
Common Name English
HYDROCHLOROTHIAZIDE IMPURITY, CHLOROTHIAZIDE- [USP]
Common Name English
CHLOROTHIAZIDE [MART.]
Common Name English
CHLOROTHIAZIDE [USP]
Common Name English
HYDROCHLOROTHIAZIDE SPECIFIED IMPURITY A [EP]
Common Name English
CHLOROTHIAZIDE [MI]
Common Name English
Classification Tree Code System Code
WHO-ATC C03AB04
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
WHO-ATC C03AA04
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
NDF-RT N0000166469
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
WHO-VATC QC03AB04
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
NCI_THESAURUS C49185
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
NDF-RT N0000175419
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
CFR 21 CFR 520.420
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
WHO-VATC QC03AA04
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
NDF-RT N0000166469
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
LIVERTOX 194
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
WHO-VATC QC03AH01
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
NDF-RT N0000175359
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
WHO-ATC C03AH01
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
Code System Code Type Description
FDA UNII
77W477J15H
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
PRIMARY
INN
636
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
PRIMARY
EVMPD
SUB06198MIG
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
PRIMARY
MESH
D002740
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
PRIMARY
WIKIPEDIA
CHLOROTHIAZIDE
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
PRIMARY
HSDB
3030
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
PRIMARY
ECHA (EC/EINECS)
200-404-9
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
PRIMARY
DRUG BANK
DB00880
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
PRIMARY
EPA CompTox
58-94-6
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
PRIMARY
LACTMED
Chlorothiazide
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
PRIMARY
CAS
58-94-6
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
PRIMARY
ChEMBL
CHEMBL842
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
PRIMARY
MERCK INDEX
M3441
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
PRIMARY Merck Index
DRUG CENTRAL
609
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
PRIMARY
RXCUI
2396
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
PRIMARY RxNorm
IUPHAR
4835
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
PRIMARY
NCI_THESAURUS
C28924
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
PRIMARY
PUBCHEM
2720
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
PRIMARY
USP_CATALOG
1121005
Created by admin on Fri Jun 25 20:35:01 UTC 2021 , Edited by admin on Fri Jun 25 20:35:01 UTC 2021
PRIMARY USP-RS