Methylchlorothiazide (0-100 μM) reduced the contraction impact by 59% and 32.3%, respectively, in the aorta of SHR, the biggest vessels to norepinephrine and arginine vasopressin (AVP), and exclusively in the endothelium-dependent manner. 1]. The contractile response to norepinephrine is inhibited by methylchlorothiazide (0-100 μM), which is removed by N-nitro-L-arginine (NOLA) but not by indomethacin [1]. Under high K+ depolarizing circumstances, methylclothiazide (100 μM) influences vascular responses to extracellular Ca2+. In solutions without Ca2+ and rich in K+, it lessens Ca2+ contracture. There was a 90.4% reduction in the maximal contracture[1].

Absorption, Distribution and Excretion
Rapid absorption after oral administration.
Thiazide diuretics are absorbed via the gastrointestinal tract, and their therapeutic effects are primarily attributed to the oral route. Absorption is relatively rapid. Most drugs show significant diuretic effects within hours of oral administration. /Thiazide Diuretics/
Generally, thiazide diuretics with longer durations of action have higher plasma protein binding and renal tubular reabsorption rates. …The drugs readily cross the placental barrier into the fetus. All thiazide diuretics are likely actively secreted in the proximal renal tubules. /Thiazide Diuretics/
Methylchlorothiazide is absorbed via the gastrointestinal tract. Information regarding the extent of absorption and distribution of methylchlorothiazide in the body is currently limited. Methylchlorothiazide is excreted unchanged in the urine.
Metabolism/Metabolites

Methylchlorothiazide is excreted unchanged in the urine.

Effects During Pregnancy and Lactation
◉ Overview of Lactation Use
There is currently no information on the content of methylchlorothiazide in breast milk. High-dose potent diuresis may reduce breast milk production. It is recommended to prioritize other low-dose diuretics over methylchlorothiazide.
◉ 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 lactating women.

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Drug Interactions Many diabetic patients using chlorpropamide or other sulfonylureas to control their blood sugar experience impaired glycemic control when any thiazide diuretic is added to their medication regimen. ...This drug interaction may occur with dimethyl acesulfame potassium, tolbutamide, and tolbutamide. /Thiazide Diuretics/
Thiazide drugs can enhance the antihypertensive effect of guanethidine, thereby reducing the dose of guanethidine and decreasing the incidence of adverse reactions. ...Betanidine and desbroquine are chemically and pharmacologically associated with guanethidine and are expected to interact with hydrochlorothiazide. /Thiazide Diuretics/
Chlorothiazine and other thiazide diuretics enhance the cardiotoxicity and neurotoxicity of lithium, therefore these drugs should not be taken concurrently. Thiazide Diuretics
...Use of diuretics (thiazides) that can increase plasma uric acid levels can interfere with uricosuric therapy...Thiazide Diuretics
For more (complete) interaction data on methylchlorothiazide (16 in total), please visit the HSDB record page.

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Non-human toxicity values
Rat intraperitoneal LD50: 2000 mg/kg
Mouse intraperitoneal LD50: 870 mg/kg
Mouse intravenous LD50: 400 mg/kg

[1]. Mechanisms of methyclothiazide-induced inhibition of contractile responses in rat aorta. Eur J Pharmacol, 2000. 408(1): p. 63-7.

[2]. Direct vascular actions of methyclothiazide and indapamide in aorta of spontaneously hypertensive rats. Fundam Clin Pharmacol, 2000. 14(4): p. 363-8.

[3]. Sasaki, S. and R.D. Bunag, Methyclothiazide attenuates salt-induced hypertension without affecting sympathetic responsiveness in Dahl rats. J Cardiovasc Pharmacol, 1983. 5(3): p. 378-83.

Therapeutic Uses
Thiazide Diuretics: Thiazide diuretics…can be used to control edema caused by premenstrual syndrome and to reduce fluid retention following the use of corticosteroids or estrogen. /Thiazide Diuretics/ Indications include congestive heart failure, cirrhosis with ascites, edema caused by corticosteroid and estrogen therapy, and certain types of renal impairment, including nephrotic syndrome, acute glomerulonephritis, and chronic renal failure. /Included in US product label; Thiazide Diuretics/ Thiazide diuretics can be used alone or as adjunctive therapy for hypertension. /Included in US product label; Thiazide Diuretics/ For more complete data on the therapeutic uses of methylchlorothiazide (10 in total), please visit the HSDB record page.

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Drug Warnings Because hypokalemia can accelerate glucose intolerance, a decrease in serum potassium levels can worsen diabetes. In cases of primary adrenal disease or increased mineralocorticoid activity due to corticosteroid treatment, diuretic therapy may lead to significant hypokalemia. /Thiazide diuretics/
Reversible elevation of blood urea nitrogen levels may occur… This prerenal azotemia is caused by a decrease in blood volume due to diuretics, resulting in decreased renal blood flow and glomerular filtration rate. …Thiazides may directly inhibit renal blood flow. /Thiazide diuretics/
Necrotizing vasculitis of the skin and kidneys has been reported in elderly patients, but its relationship with thiazide diuretics has not been confirmed. Thiazide diuretics
Thiazides should be used with caution in cases of heart failure or hypertension with significant renal impairment, as they may worsen renal insufficiency. Thiazide diuretics
For more complete data on drug warnings for methiothiazide (19 in total), please visit the HSDB records page.

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Pharmacodynamics
Methoxythiazide is a diuretic and antihypertensive drug, belonging to the benzothiadiazine (thiazide) class of drugs. The natriuretic activity of methoxythiazide per milligram is approximately 100 times that of its parent thiazide, chlorothiazide. At the maximum therapeutic dose, the diuretic/natriuretic effects of all thiazide classes are roughly the same. Like other benzothiadiazine drugs, methylchlorothiazide also has an antihypertensive effect and can be used alone or to enhance the antihypertensive effects of other drugs.

C9H11CL2N3O4S2

360.24

358.956

135-07-9

4121

White to off-white solid powder

1.6±0.1 g/cm3

597.9±60.0 °C at 760 mmHg

223-225ºC

315.4±32.9 °C

0.0±1.7 mmHg at 25°C

1.606

1.76

2

7

2

20

571

0

CESYKOGBSMNBPD-UHFFFAOYSA-N

InChI=1S/C9H11Cl2N3O4S2/c1-14-9(4-10)13-6-2-5(11)7(19(12,15)16)3-8(6)20(14,17)18/h2-3,9,13H,4H2,1H3,(H2,12,15,16)

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

Duretic; Aquatensen; Methyclothiazide

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)

DMSO : ~72 mg/mL (~199.87 mM)
H2O : < 0.1 mg/mL

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.)