Trichlormethiazide

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Cat Number

API0231526

CAS Number

133-67-5

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Product Detail Description Scientific Support Customer Q&A

CAS Number

133-67-5

EINECS

205-118-8

Storage

Store at room temperature

Synonyms

Metahydrin; Trichlormetazid; Trichlormethiazid; Diurazida; Trichlorex; 3-Dichloromethylhydrochlorothiazide; 2H-1,2,4-Benzothiadiazine-7-sulfonamide, 6-chloro-3-(dichloromethyl)-3,4-dihydro-, 1,1-dioxide; NSC-61560; DTXSID7023699

Molecular Formula

C8H8Cl3N3O4S2

Molecular Weight

380.7

Smiles

C1=C2C(=CC(=C1Cl)S(=O)(=O)N)S(=O)(=O)NC(N2)C(Cl)Cl

Appearance

White to off-white powder

Melting Point

248-250℃

Boiling Point

631.3±65.0℃(Predicted)

General Description

Trichlormethiazide is a thiazide diuretic belonging to the benzothiadiazine class, characterized by its high potency and prolonged duration of action compared to other agents in this family. It is available in oral tablet form and acts on the distal convoluted tubule of the nephron. This agent is structurally related to hydrochlorothiazide but exhibits approximately ten times the potency on a milligram basis.

Mechanism of Action

It inhibits the sodium-chloride symporter in the distal convoluted tubule, blocking the reabsorption of sodium and chloride ions. This inhibition results in osmotic diuresis with concomitant excretion of potassium and bicarbonate. The initial reduction in plasma volume lowers blood pressure, while chronic antihypertensive effects are attributed to reduced peripheral vascular resistance through direct vasodilatory mechanisms independent of volume contraction.

Application

It is indicated for the management of hypertension, either as monotherapy or in combination with other antihypertensive agents, as well as for the treatment of edema associated with congestive heart failure, hepatic cirrhosis, and renal dysfunction. Its high potency allows for lower milligram dosing compared to standard thiazides, with once-daily administration providing sustained diuretic and antihypertensive effects. As with all thiazides, electrolyte monitoring is essential during chronic use.

A dual reporter gene assay was developed to screen FDA‑approved drugs for effects on Mdr1a and Mdr1b promoter activity, which encode P‑glycoprotein at the blood‑brain barrier. Screening a 627‑drug library identified the thiazide diuretic trichlormethiazide as a novel enhancer of Mdr1 expression, along with the known inducer oltipraz and gemcitabine. Findings were validated in a blood‑brain barrier culture model and in wild‑type versus Mdr1 knockout mice. The authors conclude that this dual promoter assay effectively identifies modulators of Mdr1 expression with in vivo relevance, potentially informing strategies to manipulate blood‑brain barrier function.

Fig. 1 Characterization of Mdr1a and 1b reporter constructs. (Schulze S, et al., 2015)

References

Schulze S, et al. Identification of trichlormethiazide as a Mdr1a/b gene expression enhancer via a dual secretion-based promoter assay. Pharmacol Res Perspect. 2015; 3(1):e00109.

Does Trichlormethiazide require protection from light during storage?

Yes, it is photosensitive. Prolonged exposure to light can cause photodegradation. Store in light-resistant containers in a cool, dry place.

What is the recommended storage temperature for Trichlormethiazide?

Store at controlled room temperature, between 15°C and 25°C. Avoid excessive heat, which can accelerate decomposition.

Is Trichlormethiazide stable in alkaline conditions during formulation?

It is susceptible to hydrolysis under alkaline conditions. For solid dosage forms, the API is stable; for liquid formulations, pH control (acidic to neutral) is recommended.

How is the impurity profile of Trichlormethiazide verified for oral solid dosage forms?

We use a validated HPLC method to monitor related thiazide impurities and degradation products, ensuring compliance with USP/EP specifications.