Absorption, Distribution and Excretion
Torrazami is rapidly and well absorbed in the gastrointestinal tract. Torrazami is metabolized into five major metabolites, with a glycemic activity ranging from 0% to 70%. These metabolites are primarily excreted in the urine. Peak plasma concentrations are reached within 4–8 hours after oral administration. Torrazami is slowly absorbed; it begins to take effect 4–6 hours after a single dose and remains at a significant level for up to 15 hours. Torrazami is metabolized into several glycemic substances, most of which are excreted by the kidneys. Some metabolites with moderate activity are also excreted by the kidneys. /Excerpt from Table/ Excretion Rate (Percentage)...85–95 /Excerpt from Table/ For more complete data on the absorption, distribution, and excretion of torazami (7 types), please visit the HSDB records page.

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Metabolism/Metabolites
Torazami is metabolized into five major metabolites, with a hypoglycemic activity ranging from 0% to 70%.
Torazami is metabolized into multiple hypoglycemic substances…
Sulfonylureas are rapidly absorbed from the gastrointestinal tract, transported in the blood as highly protein-bound complexes, and undergo extensive hepatic metabolism (except for chlorpropamide). Hepatic metabolism and residual clearance vary considerably among different sulfonylureas, and these factors often alter steady-state serum concentrations. Metabolites may be active, thus there may be differences between the plasma half-life of the parent drug and the degree of hypoglycemia that occurs. /Sulfonylureas/
Active metabolites may accumulate in renal failure. /Excerpt from Table/
Although the exact metabolic pathway of toprazole is not fully understood, the drug may be metabolized in the liver into two hydroxy metabolites, p-toluenesulfonamide and p-carboxytoprazole, and one unidentified metabolite; several of these metabolites are pharmacologically active. Toprazole is primarily excreted in the urine as metabolites; a small amount is excreted unchanged in the urine. Toprazole is metabolized into five major metabolites, with a glycemic activity ranging from 0% to 70%. Excretion pathway: Toprazole is metabolized into five major metabolites, with a glycemic activity ranging from 0% to 70%. These are primarily excreted in the urine. Half-life: The mean biological half-life of this drug is 7 hours. The mean biological half-life of this drug is 7 hours. The plasma half-life is approximately 7 hours… The mean biological half-life… is 7 hours. Half-life… 7 hours / (Data from table)

Toxicity Summary
Sulfonylureas may bind to ATP-sensitive potassium channel receptors on the surface of pancreatic cells, reducing potassium conductance and causing cell membrane depolarization. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, increasing intracellular calcium concentration and thus inducing insulin secretion (exocytosis). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation Toprazole has been discontinued in the United States. Due to a lack of information on the use of toprazole during lactation, alternative medications are recommended, especially for breastfed newborns or preterm infants. Breastfed infants should be monitored for signs of hypoglycemia, such as irritability, lethargy, feeding difficulties, seizures, cyanosis, apnea, or hypothermia. If there is any concern, monitoring of the breastfed infant's blood glucose levels is recommended while the mother is on hypoglycemic medication. ◉ Effects on Breastfed Infants As of the revision date, no relevant published information was found.
◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found.

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Interactions
Drugs that may increase the risk of hypoglycemia caused by sulfonylureas include other hypoglycemic agents, sulfonamides, propranolol, salicylates, phenylbutazone, probenecid, dicumarol, chloramphenicol, monoamine oxidase inhibitors, and alcohol. Sulfonylureas
…Toluenesulfonamide…may interact with guanethidine…
The hypoglycemic activity of chlorpromazine may be enhanced by concomitant use of clofibrate. …Sulfonylureas…Toluenesulfonamide…shows similar interactions with clofibrate. Halofenadine…has been reported to enhance the hypoglycemic effect of sulfonylureas more than clofibrate.
Isoniazid may increase blood glucose levels and impair glucose tolerance. Precautions should be taken when isoniazid is used in diabetic patients who are receiving oral hypoglycemic agents (such as sulfonylureas). For more complete data on drug interactions of torazamycin (25 in total), please visit the HSDB record page.

Toluenesulfonamide is a white to off-white crystalline powder, odorless or with a slight odor. (NTP, 1992)
Toluenesulfonamide is an N-sulfonylurea drug, specifically a 1-toluenesulfonamide, in which the hydrogen atom at the 3-position of the nitrogen atom is replaced by a azircyclic heptane-1-yl group. It is a hypoglycemic agent used to treat type 2 diabetes. It has a dual effect of lowering blood sugar and blocking potassium channels.
Toluenesulfonamide is a sulfonylurea hypoglycemic agent, with similar effects and uses to chlorpropamide.
Toluenesulfonamide is a sulfonylurea drug.
Toluenesulfonamide is a medium-potency first-generation sulfonylurea hypoglycemic agent. Toluenesulfonamide can be converted into five major metabolites and excreted in the urine. On a mg basis, toluenesulfonamide is more potent than tolbutamide and similar in potency to chlorpropamide. This product may cause cholestatic jaundice.
A sulfonylurea hypoglycemic agent, with similar effects and uses to chlorpropamide.
A sulfonylurea hypoglycemic agent with similar effects and uses to chlorpromazine.

Indications

Used as an adjunct to dietary therapy to lower blood glucose levels in patients with non-insulin-dependent diabetes mellitus (Type II) whose blood glucose cannot be effectively controlled by diet alone.

Mechanism of Action

Sulfonylureas may bind to ATP-sensitive potassium channel receptors on the surface of pancreatic cells, reducing potassium conductance and leading to cell membrane depolarization. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, increasing intracellular calcium ion concentration, thereby inducing insulin secretion (exocytosis). Sulfonylureas are currently believed to act through several different mechanisms: 1. …leading to potassium permeability depolarization of pancreatic β-cell membranes. This results in the release of pre-synthesized insulin into the bloodstream, primarily occurring in patients with non-insulin-dependent diabetes mellitus. 2. …reducing basal hepatic glucose output… 3. …increasing insulin receptor binding… 4. …increasing intracellular AMP levels… 5. Increasing insulin secretion by inhibiting the release of glucagon and somatostatin from pancreatic α-cells and δ-cells.
Sulfonylureas lower blood glucose levels in patients with non-insulin-dependent diabetes mellitus (NIDDM) by directly stimulating the acute release of insulin from pancreatic β-cells through an unknown mechanism. This mechanism involves sulfonylurea receptors on β-cells. Sulfonylureas inhibit ATP-potassium channels and potassium ion efflux on the β-cell membrane, leading to β-cell depolarization and calcium ion influx, which in turn activates calmodulin, activates kinases, and releases insulin-containing granules via exocytosis, acting similarly to the effect of glucose. Insulin is a hormone that lowers blood glucose and controls the storage and metabolism of carbohydrates, proteins, and fats. Therefore, sulfonylureas are only effective in patients whose pancreas can produce insulin. /Sulfonylurea Antidiabetic Drugs/

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Therapeutic Use
Hydroxyglycemic Agents
…This potent drug does not have an antidiuretic effect and is particularly suitable for treating patients with a tendency to edema.
Sulfonylureas should only be used in adult patients with NIDDM who cannot control their diabetes through diet alone or who are unwilling or unable to take insulin after weight loss and failure of dietary control. /Sulfonylureas/
Oral hypoglycemic agents
Sulfonylureas are used as adjunctive therapy to treat and control certain types of non-insulin-dependent diabetes mellitus (NIDDM, also known as type 2 diabetes, adult-onset diabetes, ketoacidosis-resistant diabetes, or stable diabetes). NIDDM occurs in individuals with insufficient endogenous insulin secretion or who have developed endogenous insulin resistance. Before starting drug therapy, it is usually recommended to first try to control diabetes through changes in diet and exercise levels. For patients who do not respond well to diet control alone, or who require diet plus insulin therapy, especially those with a daily insulin dose not exceeding 40 USP units, sulfonylureas may be considered as monotherapy or in combination therapy. /Included in US product label; Sulfonylurea hypoglycemic agents/

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Drug Warnings
Reactions have been reported in the hematologic system (leukopenia, agranulocytosis, thrombocytopenia, pancytopenia, and hemolytic anemia), skin (rash, photosensitivity), gastrointestinal (nausea, vomiting, rare bleeding), and liver (elevated serum alkaline phosphatase, cholestatic jaundice).
...Contraindicated in diabetic patients with acidosis, ketosis, severe infection, coma, severe trauma, or major surgery.
Most reactions occur in patients over 50 years of age. Age is a risk factor for hypoglycemia, and patients with impaired liver or kidney function are more prone to hypoglycemia. Overdose, insufficient food intake, or irregular food intake may also trigger hypoglycemia.
Because the liver plays a crucial role in the metabolism of sulfonylureas and the kidneys play a crucial role in the excretion of the drugs and their metabolites, sulfonylureas are contraindicated in patients with hepatic or renal insufficiency. /Sulfonylureas/
For more complete data on drug warnings for torazamide (17 of them), please visit the HSDB record page.

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Pharmacodynamics
Torazamide is an oral sulfonylurea hypoglycemic agent. Torazamide appears to rapidly lower blood glucose by stimulating the pancreas to release insulin, an effect dependent on functioning β-cells in the islets of Langerhans. The mechanism by which torazamide lowers blood glucose with long-term administration is not fully elucidated. In patients with type 2 diabetes, the hypoglycemic effect persists despite a gradual decline in insulin secretion response after long-term use of torazamide. The mechanism of action of oral sulfonylurea hypoglycemic agents may involve extrapancreatic effects. Some patients who initially respond to oral hypoglycemic agents, including torazamide, may experience a decline in efficacy or ineffectiveness over time. On the other hand, torazamide may be effective in some patients who do not respond to one or more other sulfonylureas. In addition to its hypoglycemic effect, torazamide also produces a mild diuretic effect by enhancing the kidneys' clearance of free water.

C14H21N3O3S

311.3998

311.13

1156-19-0

5503

Crystals
WHITE TO OFF-WHITE, CRYSTALLINE POWDER

1.29g/cm3

289 °C772 mm Hg(lit.)

171-173 °C(lit.)

100 °C

1.596

3.574

2

4

3

21

431

0

S(C1C([H])=C([H])C(C([H])([H])[H])=C([H])C=1[H])(N([H])C(N([H])N1C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H])=O)(=O)=O

OUDSBRTVNLOZBN-UHFFFAOYSA-N

InChI=1S/C14H21N3O3S/c1-12-6-8-13(9-7-12)21(19,20)16-14(18)15-17-10-4-2-3-5-11-17/h6-9H,2-5,10-11H2,1H3,(H2,15,16,18)

1-(azepan-1-yl)-3-(4-methylphenyl)sulfonylurea

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 : ≥ 39 mg/mL (~125.24 mM)

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.)