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
Trichlorothiazide is absorbed via the gastrointestinal tract. Information regarding the extent of absorption and metabolic pathways of trichlorothiazide in the body is limited, but it is believed to be primarily excreted unchanged in the urine. Most chlorothiazide diuretics (CMPDs) are rapidly excreted within 3–6 hours. /Thiazide Diuretics/ Diuretic effect begins within 2 hours, peaks at 6 hours, and lasts for more than 24 hours. Thiazides are absorbed via the gastrointestinal tract, and their efficacy is primarily attributed to the oral route. Absorption is relatively rapid. Most drugs exhibit significant diuretic effects within hours of oral administration. /Thiazide Diuretics/ Generally, thiazides with longer durations of action have higher plasma protein binding rates and are reabsorbed by the renal tubules. The drug readily crosses the placental barrier into the fetus. All thiazides are likely actively secreted in the proximal renal tubules. /Thiazide Diuretics/ Biological Half-Life The half-life is 2–7 hours. /Excerpt from table/

Effects During Pregnancy and Lactation
◉ Overview of Lactation Use
There is currently no information on the content of trichlorothiazide in breast milk. High-dose potent diuresis may reduce breast milk production. It is recommended to prioritize other low-dose diuretics over trichlorothiazide.
◉ Effects on Breastfed Infants
No relevant published information was found as of the revision date.
◉ Effects on Lactation and Breast Milk
No relevant published information was found as of the revision date. The potent diuretic effects of thiazide and thiazide-like diuretics, fluid restriction, and chest binding have been used to suppress postpartum lactation. The additional effects of diuretics on these effective lactation-suppressing measures have not been studied. There are currently no data on the effects of diuretics on established continuous lactation.

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Drug Interactions Many diabetic patients using chlorpromazine or other sulfonylureas to control their blood sugar experience impaired glycemic control when any thiazide diuretic is added to their medication regimen. /Thiazide Diuretics/
…Thiazide diuretics and other drugs…can increase urine pH, thereby increasing the lipid solubility and renal tubular reabsorption of quinidine, thus prolonging its therapeutic effect. Thiazide Diuretics
…Thiazide diuretics can enhance the cardiotoxicity and neurotoxicity of lithium, therefore they should not be taken concurrently with lithium. Thiazide Drugs
Thiazide drugs can enhance the antihypertensive effect of guanethidine, thereby reducing the dose of guanethidine and decreasing the incidence of adverse reactions, especially orthostatic hypotension and exercise-related hypotension. /Thiazides/
For more complete data on interactions of trichlorothiazides (24 in total), please visit the HSDB record page.

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Non-human toxicity values
Rats oral LD50: 5600 mg/kg
Rats intravenous LD50: 920 mg/kg
Mice oral LD50: 2600 mg/kg
Mice intraperitoneal LD50: 540 mg/kg
Mice intravenous LD50: 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.

Trichlorothiazide is a benzothiadiazine compound with hydrogenation at positions 2, 3, and 4, substitution of an aminosulfonyl group at C-7, a chlorine group at C-6, a dichloromethyl group at C-3, and an S,S-dioxide at S-1. It is a sulfonamide antibiotic used as a diuretic to treat edema (including heart failure-related edema) and hypertension. It has both diuretic and antihypertensive effects. It is a benzothiadiazine and sulfonamide antibiotic. A thiazide diuretic with properties similar to hydrochlorothiazide. (Excerpt from Martindale Pharmacopoeia, 30th edition, p. 830) Trichlorothiazide is a short-acting 3-dichloromethyl derivative of hydrochlorothiazide and belongs to the thiazide diuretic class. A thiazide diuretic with properties similar to hydrochlorothiazide. (Excerpt from Martindale Pharmacopoeia, 30th Edition, p. 830)
See also: Reserpine; Trichlorothiazide (component); Dexamethasone; Trichlorothiazide (component).

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Indications
For the treatment of edema (including heart failure-related edema) and hypertension.

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Mechanism of Action
Trichlorothiazide appears to inhibit the active reabsorption of chloride ions in the ascending limb of the loop of Henle. It may also have a similar effect on sodium. These effects subsequently alter electrolyte transport in the proximal tubule. This leads to the excretion of sodium, chloride, and water, resulting in a diuretic effect. As a diuretic, trichlorothiazide inhibits the early active reabsorption of chloride in the distal tubule via sodium-chloride cotransporters, leading to increased excretion of sodium, chloride, and water. Thiazides (such as trichlorothiazide) also inhibit the transport of sodium ions across the renal tubular epithelium by binding to thiazide-sensitive sodium-chloride transporters. This leads to increased potassium excretion via the sodium-potassium exchange mechanism. The hypotensive mechanism of trichlorothiazide is not fully understood, but it may be related to its action on carbonic anhydrase in smooth muscle or on high-conductivity calcium-activated potassium channels (KCa channels) also present in smooth muscle. Benzothiadiazides have a direct effect on the transport of sodium and chloride in the renal tubules…unrelated to carbonic anhydrase. /Thiazide Diuretics/ Thiazides inhibit the reabsorption of sodium and chloride in the distal renal tubules. …As a class of drugs…they play an important role in potassium excretion resulting from increased cation secretion in the distal renal tubules. Thiazides, especially when administered intravenously for experimental purposes, may reduce glomerular filtration rate. Thiazide diuretics may reduce the excretion of uric acid in the body, thereby increasing the concentration of uric acid in the plasma. The effect of hyperuricemia is mainly due to the inhibition of renal tubular secretion of urate. Unlike most other diuretics, thiazide diuretics reduce renal calcium excretion (relative to sodium excretion) and increase magnesium excretion. Thiazide Diuretics
The nature of the chemical interaction between thiazide diuretics and the specific renal receptors responsible for the action of chlordiuresis is unclear; key enzymatic reactions have not been identified. Thiazide Diuretics
For more complete data on the mechanisms of action of trichlorothiazides (11 in total), please visit the HSDB record page.

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Therapeutic Uses
Antihypertensive drugs; Thiazide diuretics
Orally effective and long-acting thiazide diuretics and antihypertensive drugs. …Their activity is approximately 250 times that of chlorothiazides per milligram.
Thiazides…are generally the first-line drugs for the treatment of hypertension. Because thiazides cause only a limited (10%) decrease in blood pressure, they are suitable for mild cases of hypertension or as adjunctive therapy to other medications. Thiazide Diuretics
Thiazide diuretics can be used as adjunctive therapy for the treatment of congestive heart failure, cirrhosis, edema caused by corticosteroids and estrogen therapy, edema caused by various renal insufficiency…and severe edema caused by pregnancy. /Thiazide Diuretics/
For more complete data on the therapeutic uses of trichlorothiazide (11 in total), please visit the HSDB record page.

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Drug Warnings
Trichlorothiazide…because its duration of action exceeds 24 hours, it may be administered less frequently than most thiazide drugs.
Serve electrolytes should be measured regularly in all patients to detect electrolyte imbalances such as hyponatremia, hypochloremic alkalosis, and hypokalemia.
Thiazide Diuretics
Thiazide diuretics are contraindicated in patients with anuria, patients with hypersensitivity to thiazide diuretics or other sulfonamides, and healthy pregnant women with or without mild edema. …Caution should be exercised in patients with kidney disease as they may develop azotemia. Thiazide Diuretics
Patients taking thiazide diuretics long-term should have their plasma potassium levels monitored regularly. /Thiazide Diuretics/
For more complete data on the drug warnings of trichlorothiazide (11 in total), please visit the HSDB record page.

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Pharmacodynamics
Trichlorothiazide is indicated for the treatment of congestive heart failure, cirrhosis, and edema associated with corticosteroid and estrogen therapy. Trichlorothiazide can also be used to treat edema caused by various renal disorders, such as nephrotic syndrome, acute glomerulonephritis, and chronic renal failure. Trichlorothiazide can also be used to treat hypertension, both as a monotherapy and to enhance the efficacy of other antihypertensive drugs in more severe hypertension. Like other thiazides, trichlorothiazide promotes the excretion of water from the body (diuresis). Thiazides inhibit the reabsorption of sodium/chloride ions in the distal convoluted tubule of the kidney. They also lead to potassium loss and elevated serum uric acid. Thiazides are commonly used to treat hypertension, but their antihypertensive effect is not entirely attributable to their diuretic activity. Although the mechanism is not fully elucidated, thiazides have been shown to prevent hypertension-related morbidity and mortality. Thiazides induce vasodilation by activating calcium-activated potassium channels (large conductance channels) in vascular smooth muscle 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.)