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Details

Stereochemistry RACEMIC
Molecular Formula C8H8Cl3N3O4S2
Molecular Weight 380.656
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TRICHLORMETHIAZIDE

SMILES

NS(=O)(=O)C1=CC2=C(NC(NS2(=O)=O)C(Cl)Cl)C=C1Cl

InChI

InChIKey=LMJSLTNSBFUCMU-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Description

Trichloromethiazide, previously sold under the brand names of NAQUA, METAHYDRIN and TRICHLOREX, 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. Trichlormethiazide appears to block the active reabsorption of chloride and possibly sodium in the ascending loop of Henle, altering 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.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
449.0 nM [Ki]
312.0 nM [Ki]
345.0 nM [Ki]
91.0 nM [Ki]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
NAQUA

Cmax

ValueDoseCo-administeredAnalytePopulation
42.2 ng/mL
4 mg single, oral
TRICHLORMETHIAZIDE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
210.2 ng × h/mL
4 mg single, oral
TRICHLORMETHIAZIDE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
2.3 h
4 mg single, oral
TRICHLORMETHIAZIDE plasma
Homo sapiens

Doses

PubMed

Sample Use Guides

In Vivo Use Guide
Usual adult dose Diuretic or [Antidiuretic (central or nephrogenic diabetes insipidus)] Oral, 1 to 4 mg once a day, once every other day, or once a day for three to five days a week. Antihypertensive Oral, 2 to 4 mg once a day, the dosage being adjusted according to response.
Route of Administration: Oral
In Vitro Use Guide
Trichloromethiazide (100 uM) in the lumen increased net Ca2+ absorption (JCa) in isolated rabbit connecting tubules (CNT).