Glibenclamide

Glibenclamide
Clinical data
Trade names see below
Synonyms Glyburide (USAN US)
AHFS/Drugs.com International Drug Names
MedlinePlus a684058
License data
Pregnancy
category
  • AU: C
  • US: B (No risk in non-human studies)
    Routes of
    administration    		 Oral
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Protein binding Extensive
    Metabolism Hepatic hydroxylation (CYP2C9-mediated)
    Elimination half-life 10 hours
    Excretion Renal and biliary
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    ECHA InfoCard 100.030.505 Edit this at Wikidata
    Chemical and physical data
    Formula C23H28ClN3O5S
    Molar mass 494.004 g/mol
    3D model (JSmol)
    Melting point 169 to 170 °C (336 to 338 °F)
      (verify)

    Glibenclamide, also known as glyburide, 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).[1]

    Medical uses

    It is used in the treatment of type 2 diabetes.

    It is not as good as either metformin or insulin in those who have gestational diabetes.[2]

    Side effects and contraindications

    This medication is a major cause of medication-induced hypoglycemia. The risk is greater than with other sulfonylureas.[3] Cholestatic jaundice is noted.

    Glibenclamide may be not recommended in those with G6PD deficiency, as it may cause acute hemolysis.[4]

    Mechanism of action

    The medication works by binding to and inhibiting the ATP-sensitive potassium channels (KATP) inhibitory regulatory subunit sulfonylurea receptor 1 (SUR1)[5] 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 pancreatic 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.[6] Moreover, under ischemic conditions SUR1, the regulatory subunit of the KATP- and the NCCa-ATP-channels, is expressed in neurons, astrocytes, oligodendrocytes, endothelial cells[7] and by reactive microglia.[6]

    Analogs

    Additional glibenclamide structural analogs have been prepared by Ahmadi et al.[8]

    Research

    Glibenclamide improves outcome in animal stroke models by preventing brain swelling[9] and enhancing neuroprotection.[5] 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.[10]

    Trade names

    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.

    See also

    References

    1. ↑ Marble A (1971). "Glibenclamide, a new sulphonylurea: whither oral hypoglycaemic agents?". Drugs. 1 (2): 109–15. doi:10.2165/00003495-197101020-00001. PMID 4999930.
    2. ↑ Balsells, M; García-Patterson, A; Solà, I; Roqué, M; Gich, I; Corcoy, R (21 January 2015). "Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: a systematic review and meta-analysis". BMJ (Clinical research ed.). 350: h102. doi:10.1136/bmj.h102. PMC 4301599. PMID 25609400.
    3. ↑ Gangji, A. S.; Cukierman, T.; Gerstein, H. C.; Goldsmith, C. H.; Clase, C. M. (1 February 2007). "A Systematic Review and Meta-Analysis of Hypoglycemia and Cardiovascular Events: A comparison of glyburide with other secretagogues and with insulin". Diabetes Care. 30 (2): 389–394. doi:10.2337/dc06-1789. PMID 17259518.
    4. ↑ Meloni G, Meloni T (January 1996). "Glyburide-induced acute haemolysis in a G6PD-deficient patient with NIDDM". Br. J. Haematol. 92 (1): 159–60. doi:10.1046/j.1365-2141.1996.275810.x. PMID 8562390.
    5. 1 2 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 1693980. PMID 17015627.
    6. 1 2 Ortega FJ, Gimeno-Bayon J, Espinosa-Parrilla JF, Carrasco JL, Batlle M, Pugliese M, Mahy N, Rodríguez MJ (May 2012). "ATP-dependent potassium channel blockade strengthens microglial neuroprotection after hypoxia-ischemia in rats". Exp. Neurol. 235 (1): 282–96. doi:10.1016/j.expneurol.2012.02.010. PMID 22387180.
    7. ↑ 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 3434627. PMID 22714048.
    8. ↑ 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. doi:10.2174/1570193x10666140103112311. PMID 24387708.
    9. ↑ 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.
    10. ↑ 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 2742413. PMID 17673715.

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