|Systematic (IUPAC) name|
|Trade names||Diabeta, Glynase, Micronase Daonil, Semi-Daonil, Euglucon, Delmide, Glybovin Gilemal|
|Licence data||US FDA:|
|Metabolism||Hepatic hydroxylation (CYP2C9-mediated)|
|Excretion||Renal and biliary|
|Molecular mass||494.004 g/mol|
|(what is this?)|
Glibenclamide (AAN, BAN, INN), also known as glyburide (USAN), is an antidiabetic drug in a class of medications known as sulfonylureas, closely related to sulfa drugs. It was developed in 1966 in a cooperative study between Boehringer Mannheim (now part of Roche) and Hoechst (now part of Sanofi-Aventis).
It is sold in doses of 1.25, 2.5, and 5 mg, under the trade names Diabeta, Glynase, and Micronase in the United States and Daonil, Semi-Daonil, and Euglucon in the United Kingdom, and Delmide, Glybovin in India. It is also sold in combination with metformin under the trade names Glucovance, Benimet, and Glibomet, as well as Glucored and Glucored Forte (by Sun Pharmaceutical) in Russia, Belarus and other countries of the CIS.
It is used in the treatment of type 2 diabetes. As of 2011[update], it is one of only two oral antidiabetics in the World Health Organization Model List of Essential Medicines (the other being metformin). As of 2003, in the United States, it was the most popular sulfonylurea.
Side effects and contraindications
Glibenclamide may be contraindicated in those with G6PD deficiency, as it may cause acute haemolysis.
Recently published data suggest glibenclamide is associated with significantly higher annual mortality when combined with metformin than other insulin-secreting medications, after correcting for other potentially confounding patient characteristics. The safety of this combination has been questioned. Glibenclamide causes cholestasis as the major side effect.
Mechanism of action
The drug works by binding to and activating the ATP-sensitive potassium channels (KATP) inhibitory regulatory subunit sulfonylurea receptor 1 (SUR1)  in pancreatic beta cells. This inhibition causes cell membrane depolarization, opening voltage-dependent calcium channels. This results in an increase in intracellular calcium in the beta cell and subsequent stimulation of insulin release.
After a cerebral ischemic insult, the blood–brain barrier is broken and glibenclamide can reach the central nervous system. Glibenclamide has been shown to bind more efficiently to the ischemic hemisphere. Moreover, under ischemic conditions SUR1, the regulatory subunit of the KATP- and the NCCa-ATP-channels, is expressed in neurons, astrocytes, oligodendrocytes, endothelial cells and by reactive microglia.
Glibenclamide improves outcome in animal stroke models by preventing brain swelling and enhancing neuroprotection. A retrospective study showed, in type 2 diabetic patients already taking glyburide, NIH stroke scale scores on were improved on discharge compared to diabetic patients not taking glyburide.
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