Glibenclamide

Last updated

Glibenclamide
Glibenclamide.svg
Glibenclamide-4YVP-ball-and-stick.png
Clinical data
Trade names Diabeta, Glynase, Micronase, others [1]
Other namesGlyburide (USAN US)
AHFS/Drugs.com Monograph
MedlinePlus a684058
License data
Pregnancy
category
  • AU:C
Routes of
administration
By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only [2]
  • EU:Rx-only
Pharmacokinetic data
Protein binding Extensive
Metabolism Liver hydroxylation (CYP2C9-mediated)
Elimination half-life 10 hours
Excretion Kidney and bile duct
Identifiers
  • 5-chloro-N-[2-[4-(cyclohexylcarbamoylsulfamoyl)
    phenyl]ethyl]-2-methoxybenzamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.030.505 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C23H28ClN3O5S
Molar mass 494.00 g·mol−1
3D model (JSmol)
Melting point 169 to 170 °C (336 to 338 °F)
  • O=C(NC1CCCCC1)NS(=O)(=O)c2ccc(cc2)CCNC(=O)c3cc(Cl)ccc3OC
  • 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) Yes check.svgY
  • Key:ZNNLBTZKUZBEKO-UHFFFAOYSA-N Yes check.svgY
   (verify)

Glibenclamide, also known as glyburide, is an antidiabetic medication used to treat type 2 diabetes. [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 type 1 diabetes. [1] It is taken by mouth. [1]

Contents

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. [3] 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. [4] [1] It is available as a generic medication. [3] In 2021, it was the 214th most commonly prescribed medication in the United States, with more than 2 million prescriptions. [5] [6]

Medical uses

Glibenclamide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. [2]

It is not as good as either metformin or insulin in those who have gestational diabetes. [7]

Side effects

Frequently reported side effects include: nausea, heartburn, weight gain, and bloating. [8] The medication is also a major cause of medication-induced hypoglycemia. The risk is greater than with other sulfonylureas. [9]

Contraindications

Glibenclamide may be not recommended in those with G6PD deficiency, as it may cause acute hemolysis. [10]

Pregnancy and breastfeeding

It is generally not recommended during pregnancy but can be used during breastfeeding. [3]

Mechanism of action

The medication, a sulfonylurea, works by binding to and inhibiting the ATP-sensitive potassium channels (KATP) inhibitory regulatory subunit sulfonylurea receptor 1 (SUR1) [11] in pancreatic beta cells. This inhibition causes cell membrane depolarization, opening voltage-dependent calcium Channels. [12]

This results in an increase in intracellular calcium in the pancreatic beta cell and subsequent stimulation of insulin release. [13]

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. [14] Moreover, under ischemic conditions SUR1, the regulatory subunit of the KATP- and the NCCa-ATP-channels, is expressed in neurons, astrocytes, oligodendrocytes, endothelial cells [15] and by reactive microglia. [14]

As per the research papers, this sulphonylurea drugs also has extra hepatic effects. It works by inhibiting the enzyme Carnityl Acyl Transferase I (CAT-I) indirectly which is present in the mitochondria. This prevents the transport of long chain fatty acids into the mitochondria for beta-oxidation. This prevents hyperglycemia for which it is prescribed. [16] [17]

History

It was developed in 1966 in a cooperative study between Boehringer Mannheim (now part of Roche) and Hoechst (now part of Sanofi-Aventis). [18]

Society and culture

Brand names

Glibenclamide is available as a generic medication, is manufactured by many pharmaceutical companies and is sold under many brand names including Gliben-J, Daonil, [19] Diabeta, [20] 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. [21]

Related Research Articles

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<span class="mw-page-title-main">Sulfonylurea</span> Class of organic compounds used in medicine and agriculture

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K<sub>ir</sub>6.2 Protein-coding gene in the species Homo sapiens

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References

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