Glibenclamide

Not to be confused with gliclazide or glipizide.

Glibenclamide

Systematic (IUPAC) name
5-chloro-N-[2-[4-(cyclohexylcarbamoylsulfamoyl) phenyl]ethyl]-2-methoxybenzamide
Clinical data
Trade names	Diabeta, Glynase, Micronase Daonil, Semi-Daonil, Euglucon, Delmide, Glybovin, Gilemal
AHFS/Drugs.com	International Drug Names
MedlinePlus	a684058
Licence data	US FDA:link
Pregnancy category	AU: C US: B (No risk in non-human studies)
Legal status	UK: POM (Prescription only) US: ℞-only
Routes of administration	Oral
Pharmacokinetic data
Protein binding	Extensive
Metabolism	Hepatic hydroxylation (CYP2C9-mediated)
Biological half-life	10 hours
Excretion	Renal and biliary
Identifiers
CAS Number	10238-21-8 Y
ATC code	A10BB01 (WHO)
PubChem	CID: 3488
IUPHAR/BPS	2414
DrugBank	DB01016 Y
ChemSpider	3368 Y
UNII	SX6K58TVWC Y
KEGG	D00336 Y
ChEBI	CHEBI:5441 Y
ChEMBL	CHEMBL472 Y
Chemical data
Formula	C23H28ClN3O5S
Molecular mass	494.004 g/mol
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) Y Key:ZNNLBTZKUZBEKO-UHFFFAOYSA-N Y
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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).

It is sold in doses of 1.25, 2.5, 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, Glybovin in India. It is also sold in combination with metformin under the trade names Glucovance, Benimet, and Glibomet, as well as Glucored and Glucored Forte (by Sun Pharmaceutical) in Russia, Belarus and other countries of the CIS.

Medical uses

It is used in the treatment of type 2 diabetes. As of 2003, in the United States, it was the most popular sulfonylurea.

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

Side effects and contraindications

This drug is a major cause of drug-induced hypoglycemia. The risk is increased against other sulfonylureas. Cholestatic jaundice is noted.

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 (K_ATP) 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 K_ATP- and the NC_Ca-ATP-channels, is expressed in neurons, astrocytes, oligodendrocytes, endothelial cells and by reactive microglia.

Analogs

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

Research

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.

See also

• Tolbutamide
• Glipizide