Glibenclamide
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| Systematic (IUPAC) name | |
| 5-chloro-N-(4-[N-(cyclohexylcarbamoyl)sulfamoyl]phenethyl)-2-methoxybenzamide | |
| Clinical data | |
| AHFS/Drugs.com | International Drug Names |
| MedlinePlus | a684058 |
| Licence data | US FDA:link |
| Pregnancy cat. | C(AU) B(US) |
| Legal status | POM (UK) ℞-only (US) |
| Routes | Oral |
| Pharmacokinetic data | |
| Protein binding | Extensive |
| Metabolism | Hepatic hydroxylation (CYP2C9-mediated) |
| Half-life | 10 hours |
| Excretion | Renal and biliary |
| Identifiers | |
| CAS number | 10238-21-8  |
| ATC code | A10BB01 |
| PubChem | CID 3488 |
| IUPHAR ligand | 2414 |
| DrugBank | APRD00233 |
| ChemSpider | 3368 |
| UNII | SX6K58TVWC |
| KEGG | D00336 |
| ChEBI | CHEBI:5441 |
| ChEMBL | CHEMBL472 |
| Chemical data | |
| Formula | C23H28ClN3O5S |
| Mol. mass | 494.004 g/mol |
| SMILES | eMolecules & PubChem |
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Glibenclamide (INN), also known as glyburide (USAN), is an antidiabetic drug in a class of medications known as sulfonylureas, closely related to sulfa drugs. It was developed in 1966 in a cooperative study between Boehringer Mannheim (now part of Roche) and Hoechst (now part of Sanofi-Aventis).[1]
It is sold in doses of 1.25 mg, 2.5 mg 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 in India.
It is also sold in combination with metformin under the trade names Glucovance and Glibomet.
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[edit] Medical uses
It is used in the treatment of type II diabetes. As of 2007[update], it is one of only two oral antidiabetics in the World Health Organization Model List of Essential Medicines (the other being metformin).[2] As of 2003, in the United States, it was the most popular sulfonylurea.[3]
Additionally, recent research shows that glyburide improves outcome in animal stroke models by preventing brain swelling. A retrospective study showed that in type 2 diabetic patients already taking glyburide, there was improved NIH stroke scale scores on discharge compared to diabetic patients not taking glyburide. [4]
[edit] Mechanism of action
The drug works by inhibiting ATP-sensitive potassium channels[5] in pancreatic beta cells. This inhibition causes cell membrane depolarization opening voltage-dependent calcium channel. This results in an increase in intracellular calcium in the beta cell and subsequent stimulation of insulin release.
[edit] Side effects and contraindications
This drug is a major cause of drug induced hypoglycemia. Cholestatic jaundice is noted.
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.[6] Gilbenclamide causes cholestasis as the major side effect.
Glibenclamide has been demonstrated to block the protection offered by myocardial preconditioning in dogs.[7]
[edit] Synthesis
The N-acetyl derivative of β-phenethylamine is reacted with chlorosulfonic acid to form the para sulfonyl chloride derivative. This is then subjected to ammonolysis, followed by base-catalyzed removal of the acetamide. This is then acylated with 2-methoxy-5-chlorobenzoic acid chloride to give the amide intermediate. This is then reacted with cyclohexyl isocyanate to yield the sulfonylurea glibenclamide.
Hsi, R. S. P. (1973). "Synthesis of carbon-14 and tritium labeled glyburide". Journal of Labelled Compounds 9: 91. doi:10.1002/jlcr.2590090112.
[edit] References
- ^ Transdermal composition containing glibenclamide and benzyl alcohol. 3 May 2003.
- ^ (March 2007) WHO Model List of Essential MedicinesPDF (612 KiB), 15th edition, World Health Organization, p. 21. Retrieved on 2007-11-19.
- ^ Riddle MC (February 2003). "Editorial: sulfonylureas differ in effects on ischemic preconditioning--is it time to retire glyburide?". J. Clin. Endocrinol. Metab. 88 (2): 528–30. doi:10.1210/jc.2002-021971. PMID 12574174. http://jcem.endojournals.org/cgi/pmidlookup?view=long&pmid=12574174.
- ^ Kunte, H.; Schmidt, S., Eliasziw, M., del Zoppo, G. J., Simard, J. M., Masuhr, F., Weih, M., Dirnagl, U. (2 August 2007). "Sulfonylureas Improve Outcome in Patients With Type 2 Diabetes and Acute Ischemic Stroke". Stroke 38 (9): 2526–2530. doi:10.1161/STROKEAHA.107.482216.
- ^ 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. http://aac.asm.org/cgi/pmidlookup?view=long&pmid=17015627.
- ^ Monami M, Luzzi C, Lamanna C, Chiasserini V, Addante F, Desideri CM, Masotti G, Marchionni N, Mannucci E (2006). "Three-year mortality in diabetic patients treated with different combinations of insulin secretagogues and metformin". Diabetes Metab Res Rev 22 (6): 477–82. doi:10.1002/dmrr.642. PMID 16634115.
- ^ { author = Gross GJ and Auchampach JA | title = Blockade of ATP -sensitive potassium channels prevents myocardial preconditioning in dogs | journal = Circ Res | volume = 84| pages = 973–979 | year = 1992 }
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