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
Rapidly absorbed following oral administration.
Thiazides are absorbed from GI tract and owe their usefulness largely to their effectiveness by oral route. Absorption is relatively rapid. Most agents show demonstrable diuretic effect within hr after oral administration. /thiazide diuretics/
In general, thiazides with relatively long durations of action show proportionately high degrees of both binding to plasma proteins and reabsorption by renal tubules. ... Drug passes readily through placental barrier to fetus. All thiazides probably undergo active secretion in proximal tubule. /thiazide diuretics/
Methyclothiazide is absorbed from the GI tract. Little information is available on the extent of absorption and the distribution of methyclothiazide in the body. Methyclothiazide is excreted unchanged in urine.

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Metabolism / Metabolites
Methyclothiazide is excreted unchanged in urine.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the amount of methyclothiazide in breastmilk. Intense diuresis with large doses may decrease breastmilk production. Other diuretics in low doses are preferred over methyclothiazide.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information on methyclothiazide 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 the drug regimen. ... This drug interaction may occur with acetohexamide, tolazamide, and tolbutamide. /thiazide diuretics/
Thiazides enhance the antihypertensive action of guanethidine, allowing the dose of guanethidine to be reduced and decr the incidence of adverse reactions. ... Bethanidine and debrisoquin are chemically and Pharmacologically related to guanethidine and may be expected to interact with hydrochlorothiazide. /thiazide diuretics/
Chlorothiazide and other thiazide diuretics enhance the cardiotoxic and neurotoxic effects of lithium and these drugs should not be administered concurrently. /thiazide diuretics/
...Disruption of uricosuric therapy by admin of diuretic which increases plasma uric acid levels (thiazides) ... /thiazide diuretics/
For more Interactions (Complete) data for METHYCLOTHIAZIDE (16 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat ip 2000 mg/kg
LD50 Mouse ip 870 mg/kg
LD50 Mouse iv 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
Diuretics, Thiazide
Thiazides...may be used to control edema associated with premenstrual tension and to reduce fluid retention following administration of corticosteroids or estrogens. /thiazide diuretics/
Indications include edema associated with congestive heart failure, hepatic cirrhosis with ascites, corticosteroid and estrogen therapy, and some forms of renal function impairment including nephrotic syndrome, acute glomerulonephritis, and chronic renal failure. /Included in US product labeling; Thiazide diuretics/
Thiazide diuretics are indicated either alone or as adjunctive therapy in the treatment of hypertension. /Included in US product labeling; Thiazide diuretics/
For more Therapeutic Uses (Complete) data for METHYCLOTHIAZIDE (10 total), please visit the HSDB record page.

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Drug Warnings
Because hypokalemia accelerates glucose intolerance, fall in serum potassium level can aggravate diabetes. Diuretic therapy may cause pronounced hypokalemia in presence of incr mineralocorticoid activity due to primary adrenal disease...or corticosteroid therapy. /thiazide diuretics/
Reversible elevation of blood urea nitrogen level may occur... This prerenal azotemia is caused by decrease in renal blood flow and glomerular filtration rate secondary to reduction in blood volume induced by diuretic. ...thiazides may directly depress renal blood flow. /thiazide diuretics/
Necrotizing vasculitis of skin and kidney has occurred in elderly patients, but its relationship to thiazides is still unproved. /thiazide diuretics/
When cardiac decompensation or hypertension is accompanied by significant impairment of renal function, thiazides should be admin with caution because of their capacity to aggravate renal insufficiency. /thiazide diuretics/
For more Drug Warnings (Complete) data for METHYCLOTHIAZIDE (19 total), please visit the HSDB record page.

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Pharmacodynamics
Methyclothiazide, a diuretic-antihypertensive agent, is a member of the benzothiadiazine (thiazide) class of drugs. Methyclothiazide has a per mg natriuretic activity approximately 100 times that of the prototype thiazide, chlorothiazide. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic/natriuretic effects. Like other benzothiadiazines, methyclothiazide also has antihypertensive properties, and may be used for this purpose either alone or to enhance the antihypertensive action 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.)