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
THIAZIDES ARE RAPIDLY ABSORBED FROM GI TRACT... IN GENERAL, THIAZIDES WITH RELATIVELY LONG DURATIONS OF ACTION SHOW...HIGH DEGREES OF BOTH BINDING TO PLASMA PROTEINS & ARE REABSORBED TO GREATER EXTENT BY RENAL TUBULES. ... POLYTHIAZIDE.../HAS/ LONGER DURATION OF ACTION THAT IS CORRELATED WITH SLOWER EXCRETION.
IN DOGS...ABOUT 30% OF DRUG IS METABOLIZED & ITS METABOLITES ARE EXCRETED PRIMARILY IN URINE. ABOUT 60 TO 90% OF DRUG & METABOLITE ARE EXCRETED WITHIN 24 HR IN DOG; PRIMARILY IN URINE, BUT UP TO 20% MAY BE EXCRETED IN FECES.
THIAZIDES CROSS PLACENTA & APPEAR IN CORD BLOOD. /THIAZIDE DIURETICS/
THIAZIDES...APPEAR IN MILK OF NURSING MOTHER. /THIAZIDES/
STUDY OF NORMAL HUMAN SUBJECTS RECEIVING SINGLE 1 MG ORAL DOSES REVEALED MEAN PLASMA T/2 FOR ABSORPTION & ELIMINATION OF 1.2 & 25.7 HR, RESPECTIVELY. APPROX 25% OF DRUG WAS EXCRETED UNCHANGED IN THE URINE.

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Metabolism / Metabolites
YIELDS 5-CHLORO-2-METHYLSULFAMYL-4-SULFAMYLANILINE IN DOG. /FROM TABLE/

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Biological Half-Life
Half-life is approx 25 hr. /From table/

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the amount of polythiazide in breastmilk. Intense diuresis with large doses may decrease breastmilk production. Other diuretics in low doses are preferred over polythiazide.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Polythiazide 2 mg was given twice daily for 8 days beginning within 24 hours of delivery to suppress postpartum lactation. Patients also had breast binding for at least 10 days and fluid restriction. The authors reported that this technique was effective in 124 cases reviewed. There are no data on the effects of diuretics on established lactation.

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Interactions
PATIENTS RECEIVING CHLOROTHIAZIDE & RELATED DIURETICS MAY DEVELOP ELECTROLYTE DISTURBANCES (EG, PRIMARILY HYPOKALEMIA, BUT ALSO HYPOMAGNESEMIA & HYPERCALCEMIA) WHICH MAY ENHANCE THE CARDIOTOXICITY OF DIGITALIS. /THIAZIDE DIURETICS/
USE OF ENTERIC-COATED COMBINATIONS OF POTASSIUM CHLORIDE & THIAZIDE HAS BEEN ASSOC WITH HIGH INCIDENCE OF ULCERATION OF DISTAL JEJUNUM OR ILEUM. /THIAZIDE DIURETICS/
THE CONCURRENT ADMIN OF THIAZIDE DIURETICS & MONOAMINE OXIDASE INHIBITORS MAY RESULT IN HYPOTENSION. /THIAZIDE DIURETICS/
MANY DIABETIC PATIENTS REGULATED BY CHLORPROPAMIDE OR OTHER SULFONYLUREAS EXHIBIT IMPAIRED DIABETIC CONTROL WHEN ANY THIAZIDE DIURETIC IS ADDED TO THE DRUG REGIMEN. THIS EFFECT IS USUALLY, BUT NOT ALWAYS, REVERSIBLE... /THIAZIDE DIURETICS/
For more Interactions (Complete) data for POLYTHIAZIDE (22 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat ip 400 mg/kg
LD50 Dog oral 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.
A thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p826)
Polythiazide is a Thiazide Diuretic. The physiologic effect of polythiazide is by means of Increased Diuresis.
Polythiazide is a long acting benzothiadiazine sulfonamide derivative belonging to the class of the thiazide diuretics. Polythiazide is excreted mainly in its unchanged form.
A thiazide diuretic with actions and uses similar to those of HYDROCHLOROTHIAZIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p826)
See also: Polythiazide; reserpine (component of); Polythiazide; prazosin hydrochloride (component of).

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Drug Indication
Polythiazide is a thiazide diuretic used to decrease edema and decrease blood pressure.

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Mechanism of Action
As a diuretic, polythiazide inhibits active chloride reabsorption at the early distal tubule via the thiazide-sensitive Na-Cl cotransporter (TSC), resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like polythiazide 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 polythiazide 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.
DOMINANT ACTION OF THIAZIDES IS TO INCR RENAL EXCRETION OF SODIUM & CHLORIDE & ACCOMPANYING VOL OF WATER. THIS EFFECT IS VIRTUALLY INDEPENDENT OF ACID-BASE BALANCE. /BENZOTHIADIAZIDE DIURETICS/
RENAL ACTIONS OF THIAZIDE DIURETICS DECR EXTRACELLULAR FLUIDS & PLASMA VOL, CARDIAC OUTPUT, & TOTAL EXCHANGEABLE SODIUM IN INDIVIDUALS WITHOUT ANY EVIDENCE OF CARDIAC FAILURE. AT THIS STAGE, SODIUM & WATER DEPLETION APPEARS TO PROVIDE ADEQUATE BASIS FOR ANTIHYPERTENSIVE EFFECT... /BENZOTHIADIAZIDE DIURETICS/
GLOMERULAR FILTRATION RATE MAY BE REDUCED BY THIAZIDES... THIS IS PRESUMABLY RESULT OF DIRECT ACTION ON RENAL VASCULATURE. ...THIAZIDES DECR RENAL EXCRETION OF CALCIUM RELATIVE TO THAT OF SODIUM, SINCE ITS REABSORPTION IS UNAFFECTED IN DISTAL NEPHRON WHEREAS THAT OF SODIUM IS BLOCKED. /BENZOTHIADIAZIDE DIURETICS/
BECAUSE HEMODYNAMIC MEASUREMENTS INDICATE THAT PERIPHERAL VASCULAR RESISTANCE IS DECR BY THIAZIDES, DIRECT ACTION OF THESE DRUGS ON ARTERIOLAR SMOOTH MUSCLE HAS BEEN SUGGESTED. /BENZOTHIADIAZIDE DIURETICS/
For more Mechanism of Action (Complete) data for POLYTHIAZIDE (8 total), please visit the HSDB record page.

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Therapeutic Uses
Antihypertensive Agents; Diuretics, Thiazide
THIAZIDES ARE DIURETICS OF CHOICE IN MGMNT OF EDEMA DUE TO MILD-TO-MODERATE CONGESTIVE HEART FAILURE. EDEMA DUE TO CHRONIC HEPATIC OR RENAL DISEASE MAY ALSO RESPOND FAVORABLY. ...HYPERTENSIVE DISEASE... /BENZOTHIADIAZIDE DIURETICS/
ALTHOUGH THIAZIDE DIURETICS...REPORTED TO PRODUCE ELEVATION OF PLASMA RENIN ACTIVITY, CLINICAL SIGNIFICANCE OF THIS HAS NOT BEEN ESTABLISHED. ...HAVE BEEN EFFECTIVE DIURETICS IN SOME PT WITH NEPHROSIS, BUT THEIR OVERALL THERAPEUTIC USEFULNESS...UNPREDICTABLE. /THIAZIDE DIURETICS/
MOST OF THIAZIDES ARE GIVEN IN DIVIDED DAILY DOSES FOR TREATMENT OF HYPERTENSION & FOR DIURESIS. ...POLYTHIAZIDE COULD BE GIVEN LESS FREQUENTLY, SINCE...DURATION OF ACTION /IS/ LONGER THAN 24 HR.
For more Therapeutic Uses (Complete) data for POLYTHIAZIDE (12 total), please visit the HSDB record page.

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Drug Warnings
CLINICAL TOXICITY IS RELATIVELY RARE & USUALLY RESULTS FROM UNEXPECTED HYPERSENSITIVITY. /BENZOTHIADIAZIDE DIURETICS/
...NUMBER OF HYPERSENSITIVITY REACTIONS HAVE BEEN REPORTED /ONE OF SUCH IS/ PANCREATITIS...
...IF PATIENTS DEVELOPS HYPOKALEMIA WHILE TAKING THIAZIDE FOR HYPERTENSION, CLINICIAN SHOULD CONSIDER DECR DOSAGE...RATHER THAN ADDING POTASSIUM SUPPLEMENT. SPECIAL CARE IS NECESSARY TO ENSURE ADEQUATE DIETARY INTAKE OF POTASSIUM BY PATIENTS RECEIVING THIAZIDE & DIGITALIS CONCURRENTLY. /THIAZIDE DIURETICS/
IN PATIENTS, PARTICULARLY THOSE WITH HYPOTENSIVE DISEASE & DECR RENAL RESERVE, MANIFESTATIONS OF RENAL INSUFFICIENCY MAY BE AGGRAVATED AFTER INTENSIVE OR PROLONGED COURSES OF THIAZIDES THAT LEAD TO EXCESSIVE DEPLETION OF FLUID & ELECTROLYTE. /BENZOTHIADIAZIDE DIURETICS/
For more Drug Warnings (Complete) data for POLYTHIAZIDE (15 total), please visit the HSDB record page.

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Pharmacodynamics
As a thiazide diuretic, Polythiazide inhibits the sodium-chloride symporter which decreases solute reabsorption leading to a retention of water in the urine, as water normally follows solutes. More frequent urination is due to the increased loss of water that has not been retained from the body as a result of a concomitant relationship with sodium loss from the convoluted tubule. The short-term anti-hypertensive action is based on the fact that thiazides decrease preload, decreasing blood pressure

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.)