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Details

Stereochemistry ACHIRAL
Molecular Formula C7H5ClN3O4S2.Na
Molecular Weight 317.705
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CHLOROTHIAZIDE SODIUM

SMILES

[Na+].NS(=O)(=O)C1=C(Cl)C=C2N=C[N-]S(=O)(=O)C2=C1

InChI

InChIKey=CPIWHAFLBZQYLQ-UHFFFAOYSA-N
InChI=1S/C7H5ClN3O4S2.Na/c8-4-1-5-7(2-6(4)16(9,12)13)17(14,15)11-3-10-5;/h1-3H,(H2-,9,10,11,12,13);/q-1;+1

HIDE SMILES / InChI

Molecular Formula Na
Molecular Weight 22.9898
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C7H6ClN3O4S2
Molecular Weight 295.723
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including 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

1958
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

1958
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: Page: p.4
unhealthy
Health Status: unhealthy
Condition: Edema|Hypertension
Sources: Page: p.4
Disc. AE: Hypersensitivity, Azotemia...
AEs leading to
discontinuation/dose reduction:
Hypersensitivity
Azotemia
Systemic lupus erythematosus reactivation
Sources: Page: p.4
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: Page: p.4
unhealthy
Health Status: unhealthy
Condition: Edema|Hypertension
Sources: Page: p.4
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: Page: p.4
unhealthy
Health Status: unhealthy
Condition: Edema|Hypertension
Sources: Page: p.4
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: Page: p.4
unhealthy
Health Status: unhealthy
Condition: Edema|Hypertension
Sources: Page: p.4
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Drug as perpetrator​Drug as victim
PubMed

PubMed

TitleDatePubMed
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
Thiazide-induced hyponatremia.
1983 Nov
Thiazide therapy for ACTH-induced hypercalciuria and nephrolithiasis.
1992 Mar
Are certain diuretics also anticonvulsants?
2001 Oct
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
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
Do new drugs increase life expectancy? A critique of a Manhattan Institute paper.
2009 May
Formulation optimization of hydrodynamically balanced oral controlled release bioadhesive tablets of tramadol hydrochloride.
2010 Apr-Jun
Transparotid approach for mandibular condylar neck and subcondylar fractures.
2010 Dec
Buccal fat pad versus sandwich graft for treatment of oroantral defects: A comparison.
2010 Jan
Thiazide-induced hyponatremia.
2010 Jun
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
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:00:22 GMT 2023
Edited
by admin
on Fri Dec 15 15:00:22 GMT 2023
Record UNII
SN86FG7N2K
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CHLOROTHIAZIDE SODIUM
MART.   ORANGE BOOK   USAN   USP   VANDF   WHO-DD  
USAN  
Official Name English
CHLOROTHIAZIDE SODIUM [MART.]
Common Name English
6-Chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide, 1,1-dioxide, monosodium salt
Common Name English
CHLOROTHIAZIDE SODIUM [USP IMPURITY]
Common Name English
2H-1,2,4-BENZOTHIADIAZINE-7-SULFONAMIDE, 6-CHLORO-, 1,1-DIOXIDE, MONOSODIUM SALT
Common Name English
CHLOROTHIAZIDE SODIUM [USAN]
Common Name English
CHLOROTHIAZIDE SODIUM [ORANGE BOOK]
Common Name English
CHLOROTHIAZIDE SODIUM SALT [MI]
Common Name English
CHLOROTHIAZIDE SODIUM [VANDF]
Common Name English
CHLOROTHIAZIDE SODIUM SALT
MI  
Common Name English
Chlorothiazide sodium [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C49185
Created by admin on Fri Dec 15 15:00:22 GMT 2023 , Edited by admin on Fri Dec 15 15:00:22 GMT 2023
Code System Code Type Description
RXCUI
91217
Created by admin on Fri Dec 15 15:00:22 GMT 2023 , Edited by admin on Fri Dec 15 15:00:22 GMT 2023
PRIMARY RxNorm
FDA UNII
SN86FG7N2K
Created by admin on Fri Dec 15 15:00:22 GMT 2023 , Edited by admin on Fri Dec 15 15:00:22 GMT 2023
PRIMARY
SMS_ID
100000088247
Created by admin on Fri Dec 15 15:00:22 GMT 2023 , Edited by admin on Fri Dec 15 15:00:22 GMT 2023
PRIMARY
PUBCHEM
23675744
Created by admin on Fri Dec 15 15:00:22 GMT 2023 , Edited by admin on Fri Dec 15 15:00:22 GMT 2023
PRIMARY
EVMPD
SUB21994
Created by admin on Fri Dec 15 15:00:22 GMT 2023 , Edited by admin on Fri Dec 15 15:00:22 GMT 2023
PRIMARY
DRUG BANK
DBSALT000926
Created by admin on Fri Dec 15 15:00:22 GMT 2023 , Edited by admin on Fri Dec 15 15:00:22 GMT 2023
PRIMARY
CAS
7085-44-1
Created by admin on Fri Dec 15 15:00:22 GMT 2023 , Edited by admin on Fri Dec 15 15:00:22 GMT 2023
PRIMARY
DAILYMED
SN86FG7N2K
Created by admin on Fri Dec 15 15:00:22 GMT 2023 , Edited by admin on Fri Dec 15 15:00:22 GMT 2023
PRIMARY
MERCK INDEX
m3441
Created by admin on Fri Dec 15 15:00:22 GMT 2023 , Edited by admin on Fri Dec 15 15:00:22 GMT 2023
PRIMARY Merck Index
ECHA (EC/EINECS)
230-387-3
Created by admin on Fri Dec 15 15:00:22 GMT 2023 , Edited by admin on Fri Dec 15 15:00:22 GMT 2023
PRIMARY
EPA CompTox
DTXSID00221091
Created by admin on Fri Dec 15 15:00:22 GMT 2023 , Edited by admin on Fri Dec 15 15:00:22 GMT 2023
PRIMARY
NCI_THESAURUS
C65319
Created by admin on Fri Dec 15 15:00:22 GMT 2023 , Edited by admin on Fri Dec 15 15:00:22 GMT 2023
PRIMARY
ChEMBL
CHEMBL842
Created by admin on Fri Dec 15 15:00:22 GMT 2023 , Edited by admin on Fri Dec 15 15:00:22 GMT 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY