Glibenclamide

 Glibenclamide, also known as glyburide, is a medication used to treat diabetes mellitus type 2.[1] It is recommended that it be taken together with diet and exercise.[1] It may be used with other antidiabetic medication.[1] It is not recommended for use by itself in diabetes mellitus type 1.[1] It is taken by mouth.[1]

Glibenclamide
Glibenclamide.svg
Glibenclamide-4YVP-ball-and-stick.png
Clinical data
Trade namesDiabeta, Flycron, others[1]
Other namesGlyburide (USAN US)
AHFS/Drugs.comMonograph
MedlinePlusa684058
License data
  • US DailyMedGlyburide
  • US FDAGlyburide
Pregnancy
category
  • AU: C
Routes of
administration
By mouth
ATC code
  • A10BB01 (WHO)
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
  • EU: Rx-only
Pharmacokinetic data
Protein bindingExtensive
MetabolismLiver hydroxylation (CYP2C9-mediated)
Elimination half-life10 hours
ExcretionKidney and biliary
Identifiers
IUPAC name
  • 5-chloro-N-[2-[4-(cyclohexylcarbamoylsulfamoyl)
    phenyl]ethyl]-2-methoxybenzamide
CAS Number
  • 10238-21-8 check
PubChem CID
  • 3488
IUPHAR/BPS
  • 2414
DrugBank
  • DB01016 check
ChemSpider
  • 3368 check
UNII
  • SX6K58TVWC
KEGG
  • D00336 check
ChEBI
  • CHEBI:5441 check
ChEMBL
  • ChEMBL472 check
CompTox Dashboard (EPA)
  • DTXSID0037237 Edit this at Wikidata
ECHA InfoCard100.030.505 Edit this at Wikidata
Chemical and physical data
FormulaC23H28ClN3O5S
Molar mass494.00 g·mol−1
3D model (JSmol)
  • Interactive image
Melting point169 to 170 °C (336 to 338 °F)
SMILES
  • O=C(NC1CCCCC1)NS(=O)(=O)c2ccc(cc2)CCNC(=O)c3cc(Cl)ccc3OC
InChI
  • InChI=1S/C23H28ClN3O5S/c1-32-21-12-9-17(24)15-20(21)22(28)25-14-13-16-7-10-19(11-8-16)33(30,31)27-23(29)26-18-5-3-2-4-6-18/h7-12,15,18H,2-6,13-14H2,1H3,(H,25,28)(H2,26,27,29) check
  • Key:ZNNLBTZKUZBEKO-UHFFFAOYSA-N check
  (verify)

Common side effects include nausea and heartburn.[1] Serious side effects may include angioedema and low blood sugar.[1] It is generally not recommended during pregnancy but can be used during breastfeeding.[2] It is in the sulfonylureas class of medications and works by increasing the release of insulin from the pancreas.[1]

Glibenclamide was discovered in 1969 and approved for medical use in the United States in 1984.[3][1] It is available as a generic medication.[2] In 2017, it was the 174th most commonly prescribed medication in the United States, with more than three million prescriptions.[4][5]

Medical usesEdit

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.[6]

Side effectsEdit

Frequently reported side effects include: nausea, heartburn, weight gain, and bloating.[7] The medication is also a major cause of medication-induced hypoglycemia. The risk is greater than with other sulfonylureas.[8] Cholestatic jaundice is noted.

Glibenclamide may be not recommended in those with G6PD deficiency, as it may cause acute hemolysis.[9]

Pregnancy and breastfeedingEdit

It is generally not recommended during pregnancy but can be used during breastfeeding.[2]

Mechanism of actionEdit

The medication works by binding to and inhibiting the ATP-sensitive potassium channels (KATP) inhibitory regulatory subunit sulfonylurea receptor 1 (SUR1)[10] 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.[11] Moreover, under ischemic conditions SUR1, the regulatory subunit of the KATP- and the NCCa-ATP-channels, is expressed in neurons, astrocytesoligodendrocytesendothelial cells[12] and by reactive microglia.[11]

HistoryEdit

It was developed in 1966 in a cooperative study between Boehringer Mannheim (now part of Roche) and Hoechst (now part of Sanofi-Aventis).[13]

Trade namesEdit

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.[citation needed]

This article uses material from the Wikipedia article
 Metasyntactic variable, which is released under the 
Creative Commons
Attribution-ShareAlike 3.0 Unported License
.