ChemicalBook > Product Catalog > API > Hormones and the Endocrine System > Pancreatic hormone and blood sugar regulation > Glibenclamide
Basic information Hypoglycemic agents Hypoglycemic effect Precautions Chemical properties Uses Hazards & Safety Information Safety Related Supplier
Glibenclamide Chemical Properties
- Melting point:173-175°C
- Density 1.1805 (rough estimate)
- refractive index 1.6100 (estimate)
- storage temp. 2-8°C
- solubility ethanol: soluble2mg/mL
- form White solid
- pka5.3(at 25℃)
- Water Solubility Soluble in ethanol (5 mg/mL), DMSO (25 mg/mL), chloroform (1:36), methanol (1:250), and DMF. Insoluble in water.
- Merck 14,4478
- CAS DataBase Reference10238-21-8(CAS DataBase Reference)
- NIST Chemistry ReferenceGlyburide(10238-21-8)
- EPA Substance Registry SystemBenzamide, 5-chloro-N-[2-[4-[[[(cyclohexylamino)carbonyl]amino]sulfonyl]phenyl]ethyl]-2-methoxy- (10238-21-8)
Glibenclamide Usage And Synthesis
- Hypoglycemic agentsGlibenclamide belongs to the second generation oral sulfonylurea drugs with the mechanism of action being similar as tolbutamide and the hypoglycemic effect being strongest among sulfonylurea drugs. Its intensity of action is about 200 to 250 times of that of Tolbutamide. It can selectively act on the pancreatic β-cells, promote insulin secretion; can enhance the hypoglycemic effect of exogenous insulin and strengthen the post-receptor effect of insulin. It has fast oral absorption with high protein binding rate. It begins to take effect after 30 minutes with the effect being strongest at 1.5 hours and the duration of 16 to 24 hours. It has a distribution volume of 0.1L/kg, plasma protein binding rate of 90% to 95% and half-life of 4 to 8 hours. It is mainly consumed by the liver metabolism with six metabolites. Two of them are known as hydroxylated compounds with no hypoglycemic effect and is mainly excreted from the urine and a small amount is excreted by the stool. It is clinically mainly used for the treatment of mild to moderate non-insulin dependent diabetes mellitus.
Recently, an international study found that the commonly used diabetes drug glibenclamide can help the body's immune system to fight against certain bacterial infections, e.g. in the treatment of melioidosis, the mortality rate can be reduced by about half.
Melioidosis is a disease prevalent in tropical areas such as Southeast Asia and northern Australia. It is caused by Burkholderia pseudomallei with the symptoms including sepsis and pneumonia. The mortality rate is high. Diabetic patients tend to be more susceptible to melioidosis, but the mortality rate is lower compared with other patients.
- Hypoglycemic effectGlibenclamide is currently one of the most commonly used drugs for the treatment of type 2 diabetes. Because this product has fast and strong effect, so the effect after the application remarkable, being able to have good control of blood sugar; being applicable for patients of high blood sugar who get bad efficacy when treated with other sulfonyl Urea hypoglycemic agents.
Two commonly sulfonylurea oral hypoglycemic agents are glibenclamide and glimepiride, the comparison of hypoglycemic effect of them two are as follow:
(1) The effect on glucose transport and metabolism: Glibenclamide and glimepiride can stimulate the key enzymes in the glucose metabolism and improve the glucose transporter (GLUT4) translocation/dephosphorylation to promote the glucose uptake of the surrounding tissue, specifically exhibited in glycogen synthesis and increased fat formation. Glycogen synthase and 3-phosphoglycerol fatty acyltransferase are the key enzymes in glycogen and fat synthesis, and glimepiride is more active than glibenclamide in activating these key enzymes, such as for activating glycogen synthase activity, glimepiride is 2.5 times that of glibenclamide; for the capability to activate lipase, glimepiride is 1.9 times that of glibenclamide. Glimepiride increased the expression of GLUT4 on the cell membrane by inducing dephosphorylation of GLUT4.
(2) Effect on glycosylated-phosphatidylinositol-specific phospholipase (GPI-PLC): GPI is located in the outer layer of the cell membrane and participates in insulin signal transduction, which can interfere with glucose metabolism of muscle and adipocytes. GPI-PLC can shed the GPI, thereby improving the cell phosphorylation status. Insulin and sulfonylureas can activate GPI-PLC, helping muscle, adipose tissue for the uptake and transport of glucose. However, in the presence of insulin resistance, insulin itself is very difficult to activate GPI-PLC, but glimepiride can still activate the enzyme. In vitro and in vivo studies have shown that, glimepiride has the strongest pancreatic effect in sulfonylurea drugs, which can increase glucose synthesis by 2.5 times and fat synthesis by 4 times. The ratio of glimepiride to glibenclamide was 2: 1. Therefore, glimepiride has a lower secondary failure incidence than other sulfonylurea drugs.
- PrecautionsGlibenclamide should be started at low doses. During treatment, it should be regularly checked of the urine sugar, urine ketone body, urine protein and blood sugar, blood routine examination, liver and kidney function, vision, retinal blood vessels.
(1) Patients of liver and kidney dysfunction, leukopenia, sulfa allergy, pregnant women and diabetes complicated by acidosis and acute infection should be disabled.
(2) It can cause abdominal distension, abdominal pain, anorexia, nausea and other gastrointestinal reactions. It can also appear as allergy (skin erythema or urticaria), leukopenia, granulocyte deficiency, thrombocytopenia, hypoglycemia, etc., should be immediately discontinued and treated. Among them, hypoglycemia reaction is more common.
(3) Glibenclamide and other sulfonylurea hypoglycemic agents can’t be combined with thiazide diuretics or glucocorticoids.
(4) It should be avoided to taken together with anticoagulant drugs such as dicoumaroline.
(5) When combined with phenylbutazone, the hypoglycemic effect can be enhanced, causing acute hypoglycemia.
(6) Combination with sulfonamides can enhance both the effect and toxicity of glibenclamide, not suitable for use.
(7) Combination with chloramphenicol can also enhance the effect and toxicity of this product; combination of two drugs demands dose adjustment according to the patient's blood sugar levels, otherwise can cause hypoglycemic shock.
(8) Sulfonylurea drugs can enhance the toxicity of alcohol; alcohol should be avoided during treatment.
- Chemical propertiesIt appears as white crystalline powder. M.p. 168-173 ° C. It is insoluble in water, slightly soluble in ethanol, acetone and chloroform.
- UsesHypoglycemic agents with stronger effect than toluene sulfonylurea; used for the treatment of mild, non-insulin-dependent diabetes;
- Hazards & Safety InformationCategory : Toxic substances
Toxic classification: poisoning
Acute toxicity: Intraperitoneal-rat LD50: 3750 mg/kg; Oral-mouse LD50: 3250 mg/kg
Flammability Hazardous characteristics : Thermal decomposition releases toxic nitrogen oxides, sulfur oxides, chloride fumes
Storage and transport characteristics: Treasury: low temperature, ventilated and dry
Extinguishing agent : water, carbon dioxide, foam, dry powder
- Chemical PropertiesWhite or almost white, crystalline powder
- UsesGlyburide is a second generation sulfonylurea with hypoglycemic activity. Glyburide is an antidiabetic.
- UsesAn ATP-dependent KIR6 and CFTR Cl- channel blocker
- DefinitionChEBI: An N-sulfonylurea that is acetohexamide in which the acetyl group is replaced by a 2-(5-chloro-2-methoxybenzamido)ethyl group.
- brand nameMicronase (Pharmacia & Upjohn).
- General DescriptionGlyburide (glibenclamide) is 5-chloro-N-[2-[4-[[[(cyclohexylamino)carbonyl]amino]sulfonyl]phenyl]ethyl]-2-methoxybenzamide; this compound can also be named asthe urea—see preceding discussion (Diabeta, Glynase,generic). Some tablet formulations contain micronized drug(formerly Micronase, now only generic). Combinations areavailable with metformin in the United States (Glucovance,generic; tablets, mg glipizide/mg metformin as hydrochloride:1.25/250, 2.5/500, 5/500).
- General DescriptionSimilar to glipizide, glyburide, 1-[[p-[2-(5-chloro-o-anisamido)ethyl]-phenyl]sulfonyl]-3-cyclohexylurea(DiaBeta, Micronase, Glynase), is a second-generationoral hypoglycemic agent. The drug has a half-life eliminationof 10 hours, but its hypoglycemic effect remains for upto 24 hours.
- Biological ActivityATP-dependent K + channel (K ATP ) and CFTR Cl - channel blocker. Inhibits K ATP currents in the pancreas, causing an increase in intracellular Ca 2+ and insulin secretion. Inhibits recombinant CFTR Cl- channels with an IC 50 of 20 μ M.
- Company Name:GUANGZHOU CHANGTHINKING IMP.&EXP.CO.,LTD Gold
- Products Intro:Product Name:Glibenclamide
- Company Name:Jinan Zhongke Yitong Chemical Co., Ltd. Gold
- Products Intro:Product Name:Glibenclamide
- Company Name:Chengdu mingnijitai Pharmaceutical Co., Ltd Gold
- Products Intro:Product Name:Glibenclamide
- Company Name:Shanghai Boyle Chemical Co., Ltd.
- Tel:Mr Qiu:021-50182298(Demestic market) Miss Xu：021-50180596（Abroad market）
- Products Intro:Product Name:GlibenclaMide
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- Products Intro:Product Name:Glyburide, 98%