|Systematic (IUPAC) name|
|Trade names||see below|
|AHFS/Drugs.com||International Drug Names|
|Metabolism||Hepatic hydroxylation (CYP2C9-mediated)|
|Biological half-life||10 hours|
|Excretion||Renal and biliary|
|ATC code||A10BB01 (WHO)|
|Molar mass||494.004 g/mol|
Glibenclamide (AAN, BAN, INN), also known as glyburide (USAN), is an antidiabetic drug in a class of medications known as sulfonylureas, closely related to sulfonamide antibiotics. It was developed in 1966 in a cooperative study between Boehringer Mannheim (now part of Roche) and Hoechst (now part of Sanofi-Aventis).
Side effects and contraindications
Glibenclamide may be not recommended 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.
Mechanism of action
The drug works by binding to and inhibiting 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 were improved on discharge compared to diabetic patients not taking glyburide.
Glibenclamide is available as a generic, is manufactured by many pharmaceutical companies and is sold in doses of 1.25, 2.5 and 5 mg under many brand names including Gliben-J, Daonil, Diabeta, Euglucon, Gilemal, Glidanil, Glybovin, Glynase, Maninil, Micronase and Semi-Daonil. It is also available in a fixed-dose combination drug with metformin that is sold under various trade names, e.g. Bagomet Plus, Benimet, Glibomet, Gluconorm, Glucored, Glucovance, Metglib and many others.
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- Serrano-Martín X, Payares G, Mendoza-León A (December 2006). "Glibenclamide, a blocker of K+(ATP) channels, shows antileishmanial activity in experimental murine cutaneous leishmaniasis". Antimicrob. Agents Chemother. 50 (12): 4214–6. doi:10.1128/AAC.00617-06. PMC . PMID 17015627.
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- Simard JM, Woo SK, Schwartzbauer GT, Gerzanich V (September 2012). "Sulfonylurea receptor 1 in central nervous system injury: a focused review". J. Cereb. Blood Flow Metab. 32 (9): 1699–717. doi:10.1038/jcbfm.2012.91. PMC . PMID 22714048.
- Ahmadi, A; Khalili, M; Khatami, K; Farsadrooh, M; Nahri-Niknafs, B (2014). "Synthesis and investigating hypoglycemic and hypolipidemic activities of some glibenclamide analogues in rats". Mini reviews in medicinal chemistry. 14 (2): 208–13. PMID 24387708.
- 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 . PMID 16550187.
- Kunte H, Schmidt S, Eliasziw M, del Zoppo GJ, Simard JM, Masuhr F, Weih M, Dirnagl U (September 2007). "Sulfonylureas improve outcome in patients with type 2 diabetes and acute ischemic stroke". Stroke. 38 (9): 2526–30. doi:10.1161/STROKEAHA.107.482216. PMC . PMID 17673715.