In a Bluelight 2000 device, polythiazide (500 μM, 1 min) significantly causes phototoxic NHIK 3025 cell death (e.g., 325 nM) [2].

Polythiazide (oral gavage, 10 mg/kg daily for 5 days) elevates plasma cholesterol levels in cholesterol-fed C57BL/cdJ mice [3]. Polythiazide (oral, 0.4 mg/kg) exerts diuretic and diuretic effects in hypertensive dogs and rats [1].

Animal/Disease Models: Cholesterol-fed C57BL/cdJ mice [3]
Doses: 10 mg/kg
Route of Administration: po (oral gavage), one time/day for 5 days
Experimental Results: Caused an increase in plasma total cholesterol levels of approximately 13%, and increased non-HDL lipoprotein fraction.

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Animal/Disease Models: Hypertensive dogs [1]
Doses: 0.4 mg/kg
Route of Administration: Orally, one time/day for 5 days
Experimental Results: Increased excretion of sodium and chloride.

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Animal/Disease Models: Hypertensive rats [1]
Doses: 0.05, 0.1, 0.2, 0.4 mg/kg
Route of Administration: Orally, twice a day for 3 days.
Experimental Results: Demonstrated natriuretic and chloride removal effects.

Absorption, Distribution and Excretion
Thiazide drugs are rapidly absorbed from the gastrointestinal tract… Generally, thiazide drugs with a longer duration of action… have a higher binding rate to plasma proteins and are more reabsorbed by the renal tubules. …Polythiazide drugs… have an even longer duration of action, which is associated with slower excretion. In dogs… approximately 30% of the drug is metabolized, and its metabolites are primarily excreted in the urine. Approximately 60% to 90% of the drug and its metabolites are excreted from the dog within 24 hours; primarily in the urine, but up to 20% may be excreted in the feces. Thiazide drugs can cross the placental barrier and are present in umbilical cord blood. /Thiazide Diuretics/ Thiazide drugs… are present in the breast milk of lactating mothers. /Thiazide Drugs/ Studies of single oral administration of 1 mg thiazide drugs in normal human subjects showed that the mean plasma absorption half-life and elimination half-life were 1.2 hours and 25.7 hours, respectively. Approximately 25% of the drug is excreted unchanged in the urine. Metabolites/Metabolites: In dogs, it is converted to 5-chloro-2-methylsulfonyl-4-sulfonylaniline. (Data from table) Biological Half-Life: The half-life is approximately 25 hours. (Data from table)

Effects During Pregnancy and Lactation
◉ Overview of Medication Use During Lactation
There is currently no information on the content of polythiazide in breast milk. High-dose potent diuretics may reduce breast milk production. It is recommended to prioritize other low-dose diuretics over polythiazide.
◉ Effects on Breastfed Infants
As of the revision date, no relevant published information was found.
◉ Effects on Lactation and Breast Milk
To suppress postpartum lactation, patients were given 2 mg of polythiazide twice daily for 8 days, starting within 24 hours of delivery. Simultaneously, patients were required to maintain breast binding and restrict fluid intake for at least 10 days. The authors reported that this approach was effective in a retrospective study of 124 cases. There are currently no data on the effects of diuretics on breast milk in established lactation.

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Interactions
Patients taking chlorothiazide and related diuretics may experience electrolyte disturbances (e.g., primarily hypokalemia, but also hypomagnesemia and hypercalcemia), which may enhance the cardiotoxicity of digitalis. /Thiazide Diuretics/
Use of enteric-coated potassium chloride and thiazide diuretic combination preparations is associated with a high incidence of distal jejunal or ileal ulcers. Thiazide Diuretics
Concomitant use of thiazide diuretics and monoamine oxidase inhibitors may lead to hypotension. Thiazide Diuretics
Many diabetic patients using chloropropamide or other sulfonylureas to control their blood sugar experience impaired blood sugar control after adding any thiazide diuretic to their medication regimen. This effect is usually reversible, but not always… /Thiazide Diuretics/
For more (complete) data on interactions of polythiazides (22 in total), please visit the HSDB record page.

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Non-human toxicity values
Rat intraperitoneal injection LD50: 400 mg/kg
Dog oral LD50: 450 mg/kg

[1]. Pharmacological studies with polythiazide, a new diuretic and antihypertensive agent. Proc Soc Exp Biol Med. 1961 Aug-Sep;107:864-72.

[2]. Phototoxicity due to sulphonamide derived oral antidiabetics and diuretics: investigations in a cell culture model. Photodermatol Photoimmunol Photomed. 1996 Feb;12(1):1-6.

[3]. Effects of doxazosin and other antihypertensives on serum lipid levels and lipoprotein lipase in the C57BR/cdJ mouse. J Cardiovasc Pharmacol. 1989;13 Suppl 2:S11-8; discussion S18-9.

Crystals or white powder. (NTP, 1992)
Polythiazide is a benzothiadiazine drug.
A thiazide diuretic with similar action and uses to hydrochlorothiazide. (From Martindale Pharmacopoeia, 30th edition, p. 826)
Polythiazide is a thiazide diuretic. The physiological action of polythiazide is achieved by increasing diuresis.
Polythiazide is a long-acting benzothiadiazine sulfonamide derivative, belonging to the thiazide diuretic class. Polythiazide is mainly excreted unchanged.
A thiazide diuretic with similar action and uses to hydrochlorothiazide. (From Martindale Pharmacopoeia, 30th edition, p. 826)
See also: Polythiazide; Reserpine (ingredient); Polythiazides; Prazosin Hydrochloride (ingredient).

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Drug Indications
Polythiazides are thiazide diuretics used to reduce edema and lower blood pressure.

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Mechanism of Action
As a diuretic, polythiazides increase the excretion of sodium, chloride, and water by inhibiting the early active reabsorption of chloride ions in the distal renal tubules via thiazide-sensitive sodium-chloride cotransporters (TSCs). Thiazides (such as polythiazides) also inhibit the transtubular transport of sodium ions by binding to thiazide-sensitive sodium-chloride cotransporters. This leads to increased potassium excretion via the sodium-potassium exchange mechanism. The hypotensive mechanism of polythiazides may be through their action on carbonic anhydrase in smooth muscle or through their action on high-conductivity calcium-activated potassium channels (KCa channels), which are also present in smooth muscle. The primary action of thiazides is to increase the renal excretion of sodium, chloride, and associated water. This effect is almost unaffected by acid-base balance. /Benzothiazine Diuretics/
The renal effects of thiazide diuretics can reduce extracellular fluid and plasma volume, cardiac output, and total exchangeable sodium content in individuals without heart failure. At this stage, the consumption of sodium and water appears to provide a sufficient basis for the antihypertensive effect…/Benzothiazine diuretics/
Thiazide drugs can reduce glomerular filtration rate… This is likely due to their direct effect on renal blood vessels. …Thiazide drugs reduce renal calcium excretion relative to sodium, because calcium reabsorption in distal nephrons is unaffected, while sodium reabsorption is blocked. Benzothiazine diuretics
Since hemodynamic measurements indicate that thiazide drugs reduce peripheral vascular resistance, it is speculated that these drugs have a direct effect on arteriolar smooth muscle. Benzothiazine diuretics
For more complete data on the mechanisms of action of polythiazides (8 in total), please visit the HSDB record page.

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Therapeutic Uses
Antihypertensive drugs; Thiazide diuretics
Thiazide diuretics are the first-line diuretics for treating edema caused by mild to moderate congestive heart failure. Edema caused by chronic liver or kidney disease may also be well treated. ...Hypertension.../Benzothiazine Diuretics/
Although there are reports of thiazide diuretics increasing plasma renin activity, their clinical significance is not yet established. ...Effective in some patients with kidney disease, but overall efficacy is difficult to predict. /Thiazide Diuretics/
Most thiazide drugs are taken in divided doses for the treatment of hypertension and diuresis. Because the effects of polythiazides last for more than 24 hours, the frequency of administration can be reduced.
For more complete data on the therapeutic uses of polythiazides (12 in total), please visit the HSDB record page.

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Drug Warnings
Clinical toxicity is relatively rare and usually results from unexpected hypersensitivity reactions. Benzothiazine Diuretics
...Several hypersensitivity reactions have been reported, one of which is pancreatitis...
...If a patient develops hypokalemia while taking thiazide diuretics to treat hypertension, clinicians should consider reducing the dose rather than supplementing potassium. Patients taking thiazide diuretics and digitalis concurrently must be carefully monitored to ensure adequate potassium intake. Thiazide diuretics: In patients, especially those with hypotension and impaired renal reserve, long-term or high-dose use of thiazide diuretics can lead to excessive loss of fluids and electrolytes, thus exacerbating symptoms of renal insufficiency. Benzothiadiazine diuretics: For more complete data on drug warnings for polythiazides (15 in total), please visit the HSDB record page.

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Pharmacodynamics
As a thiazide diuretic, polythiazides inhibit sodium-chloride cotransporters, thereby reducing solute reabsorption and leading to water retention in the urine, as water is normally excreted with the solute. Urinary frequency is due to increased excretion of unretained water caused by sodium loss in the renal tubules. The short-term hypotensive effect of thiazide diuretics is based on their mechanism of lowering blood pressure by reducing preload.

C11H13CLF3N3O4S3

439.8672

438.971

346-18-9

346-18-9

4870

WHITE, CRYSTALLINE POWDER
CRYSTALS FROM ISOPROPANOL

1.598g/cm3

580.1ºC at 760mmHg

202.5°

304.7ºC

1.566

4.592

2

11

4

25

692

0

CN1C(CSCC(F)(F)F)NC2=C(C=C(C(=C2)Cl)S(=O)(=O)N)S1(=O)=O

CYLWJCABXYDINA-UHFFFAOYSA-N

InChI=1S/C11H13ClF3N3O4S3/c1-18-10(4-23-5-11(13,14)15)17-7-2-6(12)8(24(16,19)20)3-9(7)25(18,21)22/h2-3,10,17H,4-5H2,1H3,(H2,16,19,20)

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

P-2525; NSC-108161; Polythiazide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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