Rats that are given triclothiazide (1 mg/kg; oral; once) excrete more potassium and salt and produce more urine [1]. High-salt (HS) rats receiving angiotensin II showed a considerable reduction in mean arterial pressure (MAP) over the course of 24 hours when triclothiazide (10 mg/kg, i.v.; daily for 5 days) was administered; however, the MAP of any other group was unaffected[2].

Animal/Disease Models: Male Wistar rats, body weight 170-300 g[1]
Doses: 1 mg/kg
Route of Administration: Orally, once.
Experimental Results: Potassium excretion in normal rats increased Dramatically. Urinary output, sodium and potassium excretion increased Dramatically in cisplatin-induced ARF (acute renal failure) rats.

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Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat (350-450 g) [2]
Doses: 10 mg/kg
Route of Administration: Daily intravenous (iv) (iv)injection for 15 days
Experimental Results: The combination of angiotensin II and high salt increased the MAP drops Dramatically for admissions.

Absorption, Distribution and Excretion
Trichlormethiazide is absorbed from the GI tract. Little information is available on the extent of absorption and the fate of trichlormethiazide in the body, although it is believed to be excreted principally as unchanged drug in urine.
MOST CMPD ARE RAPIDLY EXCRETED WITHIN 3-6 HR. /THIAZIDE DIURETICS/
DIURESIS OCCURS WITHIN 2 HR, REACHES PEAK IN 6 HR, & LASTS MORE THAN 24 HR.
THIAZIDES ARE ABSORBED FROM GI TRACT & OWE THEIR USEFULNESS LARGELY TO THEIR EFFECTIVENESS BY ORAL ROUTE. ABSORPTION IS RELATIVELY RAPID. MOST AGENTS SHOW DEMONSTRABLE DIURETIC EFFECT WITHIN HR AFTER ORAL ADMIN. /THIAZIDE DIURETICS/
IN GENERAL, THIAZIDES WITH RELATIVELY LONG DURATIONS OF ACTION SHOW PROPORTIONATELY HIGH DEGREE OF BINDING TO PLASMA PROTEINS & ARE REABSORBED... BY RENAL TUBULES. ... DRUG PASSES READILY THROUGH PLACENTAL BARRIER TO FETUS. ALL THIAZIDES PROBABLY UNDERGO ACTIVE SECRETION IN PROXIMAL TUBULE. /THIAZIDE DIURETICS/

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Biological Half-Life
Half-life is 2-7 hr. /From table/

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the amount of trichlormethiazide in breastmilk. Intense diuresis with large doses may decrease breastmilk production. Other diuretics in low doses are preferred over trichlormethiazide.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information on trichlormethiazide was not found as of the revision date. Intense diuresis with thiazides and thiazide-like diuretics, fluid restriction and breast binding have been used to suppress postpartum lactation.The added contribution of the diuretic to these measures, which are effective in suppressing lactation, has not been studied. There are no data on the effects of diuretics on established, ongoing lactation.

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Interactions
MANY DIABETIC PATIENTS REGULATED BY CHLORPROPAMIDE OR OTHER SULFONYLUREAS EXHIBIT IMPAIRED DIABETIC CONTROL WHEN ANY THIAZIDE DIURETIC IS ADDED TO DRUG REGIMEN. /THIAZIDE DIURETICS/
...DRUGS SUCH AS...THIAZIDE DIURETICS...WHICH INCR URINARY PH, MAY SERVE TO INCR LIPID SOLUBILITY & TUBULAR REABSORPTION OF QUINIDINE & THUS PROLONG ITS THERAPEUTIC EFFECTS. /THIAZIDE DIURETICS/
...THIAZIDE DIURETICS ENHANCE CARDIOTOXIC & NEUROTOXIC EFFECTS OF LITHIUM & THESE DRUGS SHOULD NOT BE ADMINISTERED CONCURRENTLY. /THIAZIDES/
THIAZIDES ENHANCE ANTIHYPERTENSIVE ACTION OF GUANETHIDINE, ALLOWING DOSE OF GUANETHIDINE TO BE REDUCED & DECR INCIDENCE OF ADVERSE REACTIONS, PARTICULARLY ORTHOSTATIC & EXERCISE-ASSOC HYPOTENSION. /THIAZIDES/
For more Interactions (Complete) data for TRICHLORMETHIAZIDE (24 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 RAT ORAL 5600 MG/KG
LD50 Rat iv 920 mg/kg
LD50 Mouse oral 2600 mg/kg
LD50 Mouse ip 540 mg/kg
LD50 Mouse iv 750 mg/kg

[1]. K Yao, et al. Diuretic effects of KW-3902, a novel adenosine A1-receptor antagonist, in various models of acute renal failure in rats. Jpn J Pharmacol. 1994 Apr;64(4):281-8.
[2]. J R Ballew, et al. Characterization of the antihypertensive effect of a thiazide diuretic in angiotensin II-induced hypertension. J Hypertens. 2001 Sep;19(9):1601-6.

Trichlormethiazide is a benzothiadiazine, hydrogenated at positions 2, 3 and 4 and substituted with an aminosulfonyl group at C-7, a chloro substituent at C-6 and a dichloromethyl group at C-3 and with S-1 as an S,S-dioxide. A sulfonamide antibiotic, it is used as a diuretic to treat oedema (including that associated with heart failure) and hypertension. It has a role as a diuretic and an antihypertensive agent. It is a benzothiadiazine and a sulfonamide antibiotic.
A thiazide diuretic with properties similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p830)
Trichlormethiazide is a short-acting, 3-dichloromethyl derivative of hydrochlorothiazide, belonging to the class of thiazide diuretics.
A thiazide diuretic with properties similar to those of HYDROCHLOROTHIAZIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p830)
See also: Reserpine; trichlormethiazide (component of); Dexamethasone; Trichlormethiazide (component of).

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Drug Indication
Used in the treatment of oedema (including that associated with heart failure) and hypertension.

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Mechanism of Action
Trichlormethiazide seemingly appears to inhibit the active reabsorption of chloride in the ascending loop of Henle. Additionally, it may also do the same for sodium. These actions subsequently alter 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.
...BENZOTHIADIAZIDES HAVE DIRECT EFFECT ON RENAL TUBULAR TRANSPORT OF SODIUM & CHLORIDE...INDEPENDENT OF ANY EFFECT ON CARBONIC ANHYDRASE. /THIAZIDE DIURETICS/
THIAZIDES INHIBIT REABSORPTION OF SODIUM &...CHLORIDE IN DISTAL SEGMENT. ... AS CLASS...HAVE IMPORTANT ACTION ON EXCRETION OF POTASSIUM THAT RESULTS FROM INCR SECRETION OF CATION BY DISTAL TUBULE. ... GLOMERULAR FILTRATION RATE MAY BE REDUCED BY THIAZIDES, PARTICULARLY WITH IV ADMIN FOR EXPTL PURPOSES. /THIAZIDE DIURETICS/
...MAY DECR EXCRETION OF URIC ACID IN MAN, THUS INCR ITS CONCN IN PLASMA. HYPERURICEMIC EFFECT RESULTS PRIMARILY FROM INHIBITION OF TUBULAR SECRETION OF URATE. ... UNLIKE MOST OTHER NATRIURETIC AGENTS...DECR RENAL EXCRETION OF CALCIUM RELATIVE TO THAT OF SODIUM... /ENHANCE/ EXCRETION OF MAGNESIUM... /THIAZIDE DIURETICS/
NATURE OF CHEM INTERACTION BETWEEN THIAZIDES & SPECIFIC RENAL RECEPTORS RESPONSIBLE FOR CHLORURETIC EFFECT IS NOT KNOWN; NO CRITICAL ENZYMATIC REACTIONS HAVE BEEN IDENTIFIED. /THIAZIDE DIURETICS/
For more Mechanism of Action (Complete) data for TRICHLORMETHIAZIDE (11 total), please visit the HSDB record page.

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Therapeutic Uses
Antihypertensive Agents; Diuretics, Thiazide
ORALLY EFFECTIVE & LONG-ACTING DIURETIC & ANTIHYPERTENSIVE OF THIAZIDE CLASS. ... ON MG BASIS, IT IS APPROX 250 TIMES MORE ACTIVE THAN CHLOROTHIAZIDE.
THIAZIDE DRUGS...USUALLY FIRST DRUG TO BE EMPLOYED IN TREATMENT OF HYPERTENSION. SINCE THIAZIDES INDUCE ONLY LIMITED (10%) REDN IN BLOOD PRESSURE THEY ARE USEFUL EITHER IN MILD CASES OF HYPERTENSION OR AS ADJUNCTIVE THERAPY TO OTHER DRUGS. /THIAZIDE DIURETICS/
THIAZIDE DIURETICS ARE EFFECTIVE AS ADJUNCTIVE THERAPY IN EDEMA ASSOC WITH CONGESTIVE HEART FAILURE, HEPATIC CIRRHOSIS, & CORTICOSTEROID & ESTROGEN THERAPY, AS WELL AS EDEMA DUE TO VARIOUS FORMS OF RENAL DYSFUNCTION...& SEVERE EDEMA DUE TO PREGNANCY. /THIAZIDE DIURETICS/
For more Therapeutic Uses (Complete) data for TRICHLORMETHIAZIDE (11 total), please visit the HSDB record page.

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Drug Warnings
TRICHLORMETHIAZIDE...COULD BE GIVEN LESS FREQUENTLY /THAN MOST OF THIAZIDES/, SINCE...DURATION OF ACTION LONGER THAN 24 HR.
PERIODIC SERUM ELECTROLYTE DETERMINATION SHOULD BE DONE ON ALL PATIENTS IN ORDER TO DETECT ELECTROLYTE IMBALANCE SUCH AS HYPONATREMIA, HYPOCHLOREMIC ALKALOSIS, & HYPOKALEMIA. /THIAZIDE DIURETICS/
THIAZIDE DIURETICS ARE CONTRAINDICATED IN ANURIA, PATIENTS HYPERSENSITIVE TO THESE & OTHER SULFONAMIDE DRUGS, & IN OTHERWISE HEALTHY PREGNANT WOMEN WITH OR WITHOUT MILD EDEMA. ...SHOULD BE USED WITH CAUTION IN PATIENTS WITH RENAL DISEASE, SINCE THEY MAY PPT AZOTEMIA. /THIAZIDE DIURETICS/
PLASMA POTASSIUM CONCN SHOULD BE DETERMINED PERIODICALLY IN PATIENTS WHO RECEIVE THIAZIDE DIURETICS FOR EXTENDED PERIODS. /THIAZIDE DIURETICS/
For more Drug Warnings (Complete) data for TRICHLORMETHIAZIDE (11 total), please visit the HSDB record page.

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Pharmacodynamics
Trichloromethiazide 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.

C8H8CL3N3O4S2

380.639

378.902

133-67-5

Trichlormethiazide sodium;91996-54-2

5560

CRYSTALS FROM METHANOL + ACETONE + WATER
WHITE, CRYSTALLINE POWDER

1.7±0.1 g/cm3

631.3±65.0 °C at 760 mmHg

248-250ºC

335.6±34.3 °C

0.0±1.8 mmHg at 25°C

1.625

0.24

3

7

2

20

571

0

ClC([H])(C1([H])N([H])C2=C([H])C(=C(C([H])=C2S(N1[H])(=O)=O)S(N([H])[H])(=O)=O)Cl)Cl

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)

6-chloro-3-(dichloromethyl)-1,1-dioxo-3,4-dihydro-2H-1λ6,2,4-benzothiadiazine-7-sulfonamide

Trichlormethiazide; BRN0629145 BRN-0629145; BRN 0629145

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~150 mg/mL (~394.05 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.57 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.57 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)