|Systematic (IUPAC) name|
|Trade names||Diabeta, Glynase, Micronase Daonil, Semi-Daonil, Euglucon, Delmide|
|Licence data||US FDA:|
|Pregnancy cat.||C (AU) B (US)|
|Legal status||POM (UK) ℞-only (US)|
|Metabolism||Hepatic hydroxylation (CYP2C9-mediated)|
|Excretion||Renal and biliary|
|Mol. mass||494.004 g/mol|
|(what is this?)|
Glibenclamide (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 mg, 2.5 mg 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 in India.
It is also sold in combination with metformin under the trade names Glucovance, Benimet and Glibomet.
Mechanism of action
The drug works by binding to and activating the sulfonylurea receptor 1 (SUR1), the regulatory subunit of the ATP-sensitive potassium channels (KATP) in pancreatic beta cells. This inhibition causes cell membrane depolarization opening voltage-dependent calcium channel. 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.
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.
Additionally, recent research shows that glibenclamide improves outcome in animal stroke models by preventing brain swelling and enhancing neuroprotection. A retrospective study showed that in type 2 diabetic patients already taking glyburide, NIH stroke scale scores on were improved on discharge compared to diabetic patients not taking glyburide.
Side effects and contraindications
Glibenclamide may be contraindicated in for 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.
Glibenclamide has been demonstrated to block the protection offered by myocardial preconditioning in dogs.
The N-acetyl derivative of β-phenethylamine is reacted with chlorosulfonic acid to form the para sulfonyl chloride derivative. This is then subjected to ammonolysis, followed by base-catalyzed removal of the acetamide. This is then acylated with 2-methoxy-5-chlorobenzoic acid chloride to give the amide intermediate. This is then reacted with cyclohexyl isocyanate to yield the sulfonylurea glibenclamide.
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- Simard JM, Chen M, Tarasov KV, Bhatta S, Ivanova S, Melnitchenko L, Tsymbalyuk N, West GA, Gerzanich V (April 2006). "Newly expressed SUR1-regulated NC(Ca-ATP) channel mediates cerebral edema after ischemic stroke". Nat. Med. 12 (4): 433–40. doi:10.1038/nm1390. PMC 2740734. PMID 16550187.
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