Carbutamide targets the ATP-sensitive potassium (KATP) channels on pancreatic beta cells. By binding to the sulfonylurea receptor (SUR1) subunit of the KATP channel, it inhibits potassium efflux, leading to depolarization of the cell membrane. This depolarization opens voltage-gated calcium channels, allowing calcium influx, which triggers insulin exocytosis. This mechanism increases insulin secretion from pancreatic beta cells, thereby lowering blood glucose levels.

In vitro, carbutamide stimulates insulin secretion from isolated pancreatic islets or beta cell lines in a dose-dependent manner. Its activity is assessed by measuring insulin release into the culture medium after treatment with various concentrations of the compound. The compound's potency is characterized by its ability to inhibit KATP channel activity and promote insulin secretion. Specific IC50 values for KATP channel inhibition are not detailed in the provided search results.

Cardinamide is a derivative of sulfonylurea that, when administered orally to normal animals, can result in hypoglycemia [2].
In vivo, carbutamide is administered orally to lower blood glucose levels in patients with type 2 diabetes. It was one of the first oral hypoglycemic agents used clinically. The compound's efficacy in reducing blood glucose has been demonstrated in numerous clinical studies. However, its use has been largely superseded by newer sulfonylureas (e.g., glibenclamide, gliclazide, glimepiride) with improved safety and efficacy profiles.

The in vitro activity of carbutamide is assessed using insulin secretion assays. Pancreatic islets or beta cell lines (e.g., INS-1, MIN6) are cultured in appropriate media and treated with various concentrations of carbutamide (typically 1-1000 μM) for 1-24 hours. Insulin levels in the culture medium are measured by ELISA or radioimmunoassay. For KATP channel studies, patch-clamp electrophysiology is used to measure channel activity in beta cells treated with carbutamide.

For cellular assays, pancreatic beta cell lines are cultured in appropriate media and treated with various concentrations of carbutamide for defined periods. Insulin secretion is measured by ELISA. Cell viability is assessed using MTT or CellTiter-Glo assays to ensure that observed effects are not due to cytotoxicity. For mechanistic studies, the effect on intracellular calcium levels can be assessed using calcium-sensitive fluorescent dyes (e.g., Fura-2, Fluo-4).

In vivo, carbutamide is administered orally to patients or animal models. In diabetic animal models (e.g., streptozotocin-induced diabetic rats), the compound is administered at various doses, and blood glucose levels are measured at regular intervals. Glucose tolerance tests can be performed to assess the compound's effect on glucose metabolism. In clinical studies, the compound's efficacy and safety are evaluated through blood glucose monitoring and assessment of adverse effects.

Absorption, Distribution and Excretion
Sulfonylureas are readily absorbed from the gastrointestinal tract. For clinical application, the most important difference between sulfonylureas lies in their duration of action… /Sulfonylureas/ Sulfonylureas primarily bind to plasma proteins and are distributed in the extracellular space. /Sulfonylureas/

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Metabolism/Metabolites …In the human body, approximately one-third of the excreted dose exists as N-acetylated metabolites. Significant species differences have been found; rabbits produce large amounts of acetyltransferases (AMTs), while monkeys and dogs have very low or no acetylation capacity, and humans are at an intermediate level. These are hydroxylated in the liver into active and inactive products, almost entirely excreted in the urine. /Sulfonylureas/
Carbutamide has a molecular weight of 285.36 g/mol and a molecular formula of C12H19N3O3S. It is a sulfonylurea compound with moderate lipophilicity. The compound is absorbed after oral administration and is metabolized in the liver. Its half-life is approximately 5-10 hours. The compound is excreted in urine. Specific pharmacokinetic parameters are not detailed in the provided search results.

Interactions
Sodium carbonate can reduce the teratogenic and lethal effects of drugs in rats. Drugs that may increase the risk of hypoglycemia caused by sulfonylureas include other hypoglycemic agents, sulfonamides, propranolol, salicylates, clofibrate, phenylbutazone, probenecid, dicumarol, chloramphenicol, monoamine oxidase inhibitors, and alcohol. /Sulfonylureas/ Alcohol and salicylates may induce hypoglycemic coma in patients taking sulfonylureas due to their direct hypoglycemic effects. Propranolol enhances the hypoglycemic effect of sulfonylureas by interfering with glycogenolysis and glucagon release. /Sulfonylureas/ Simultaneous infusion of a second drug that displaces sulfonylureas in the pancreas can alter sulfonylurea-mediated insulin secretion. Therefore, drug interactions at target organs or receptor sites should be understood to provide adequate drug therapy. For more complete data on interactions of 1-butyl-3-sulfonylureas (a total of 8), please visit the HSDB record page.
Carbutamide can cause hypoglycemia as a major side effect, which can be severe and prolonged. Other adverse effects include gastrointestinal disturbances, skin reactions (rash, photosensitivity), and hematological effects (leukopenia, agranulocytosis). The compound has been associated with a higher risk of severe hypoglycemia compared to newer sulfonylureas. It is contraindicated in patients with renal or hepatic impairment, and in patients with a history of sulfonylurea hypersensitivity.

[1]. Carbutamide--the first oral antidiabetic. A retrospect. Exp Clin Endocrinol Diabetes. 1998;106(2):149-51.

[2]. Pharmacology of carbutamide (p-aminophenylsulfonyl butylcarbamide). J Pharmacol Exp Ther. 1957 Apr;119(4):468-78.

Carbutamide is a sulfonamide compound, belonging to the benzene family. Carbutamide is a first-generation sulfonylurea drug with hypoglycemic activity. It was one of the earliest sulfonylurea compounds used, but was withdrawn from the market due to its myelotoxicity. The drug has a relatively long half-life. It is a sulfonylurea antidiabetic drug with similar effects and uses to chloropropionamide. (Excerpt from Martindale Pharmacopoeia, 30th edition, page 277) Mechanism of Action: Sulfonylureas stimulate insulin secretion from pancreatic islet tissue. ...Sulfonylureas cause β-cell degranulation, a phenomenon associated with an increased rate of insulin secretion. ...They are effective in insulin-independent diabetic patients whose pancreas still retains the ability to secrete insulin. /Sulfonylureas/ Therapeutic Uses: Hypoglycemic Drugs (Veterinary): Adding carbadamine to the diet of rats for 10-14 days resulted in a significant antithyroid effect. It reduces the uptake of iodine (131) by the thyroid gland and reduces the synthesis of thyroxine. Carbaamide… is an oral sulfonamide hypoglycemic agent used to treat diabetes… Sulfonylureas are only used in patients with insulin-independent diabetes who cannot be treated with diet alone. Sulfonylureas Hypoglycemic Agents

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Drug Warnings
Hematologic (leukopenia, agranulocytosis, thrombocytopenia, pancytopenia, and hemolytic anemia), skin (rash, photosensitivity), gastrointestinal (nausea, vomiting, rare bleeding), and hepatic (elevated serum alkaline phosphatase, cholestatic jaundice) reactions have been reported. Sulfonylureas To date, increased cardiovascular mortality during sulfonylurea treatment is its main toxic effect. Sulfonylureas 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. Alcohol intolerance has occasionally occurred in patients taking sulfonylureas. Sulfonylureas are not recommended for pregnant women. Animal studies have shown that high doses of sulfonylureas can cause birth defects. /Sulfonylureas/ For more complete data on drug warnings for 1-butyl-3-sulfonylureas (7 in total), please visit the HSDB records page.
Carbutamide is a first-generation sulfonylurea that was introduced in the 1950s for the treatment of type 2 diabetes. It played a pioneering role in the development of oral hypoglycemic agents. However, its use has been largely discontinued due to the availability of newer, safer, and more effective sulfonylureas. The compound is not commonly used clinically and is primarily of historical interest. It is available from chemical suppliers for research purposes.

C11H17N3O3S

271.33598

271.099

339-43-5

9564

Crystals

1.266g/cm3

144-145ºC

1.564

3.5

3

4

5

18

356

0

NC1C=CC(S(NC(NCCCC)=O)(=O)=O)=CC=1

VDTNNGKXZGSZIP-UHFFFAOYSA-N

InChI=1S/C11H17N3O3S/c1-2-3-8-13-11(15)14-18(16,17)10-6-4-9(12)5-7-10/h4-7H,2-3,8,12H2,1H3,(H2,13,14,15)

1-(4-aminophenyl)sulfonyl-3-butylurea

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 : ~50 mg/mL (~184.27 mM)

Solubility in Formulation 1: ≥ 2.17 mg/mL (8.00 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (7.67 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (7.67 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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