Not to be confused with gliclazide or glipizide.
Glibenclamide
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| Clinical data |
| Trade names |
see below |
| Synonyms |
Glyburide (USAN US) |
| AHFS/Drugs.com |
International Drug Names |
| MedlinePlus |
a684058 |
| License data |
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Pregnancy
category |
- AU: C
- US: B (No risk in non-human studies)
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Routes of
administration |
Oral |
| ATC code |
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| Legal status |
| Legal status |
- UK: POM (Prescription only)
- US: ℞-only
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| Pharmacokinetic data |
| Protein binding |
Extensive |
| Metabolism |
Hepatic hydroxylation (CYP2C9-mediated) |
| Biological half-life |
10 hours |
| Excretion |
Renal and biliary |
| Identifiers |
IUPAC name
- 5-chloro-N-[2-[4-(cyclohexylcarbamoylsulfamoyl)
phenyl]ethyl]-2-methoxybenzamide
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| CAS Number |
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| PubChem CID |
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| IUPHAR/BPS |
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| DrugBank |
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| ChemSpider |
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| UNII |
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| KEGG |
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| ChEBI |
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| ChEMBL |
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| ECHA InfoCard |
100.030.505 |
| Chemical and physical data |
| Formula |
C23H28ClN3O5S |
| Molar mass |
494.004 g/mol |
| 3D model (JSmol) |
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SMILES
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O=C(NC1CCCCC1)NS(=O)(=O)c2ccc(cc2)CCNC(=O)c3cc(Cl)ccc3OC
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InChI
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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
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Key:ZNNLBTZKUZBEKO-UHFFFAOYSA-N Y
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| (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]
Contents
- 1 Medical uses
- 2 Side effects and contraindications
- 3 Mechanism of action
- 4 Analogs
- 5 Research
- 6 Trade names
- 7 See also
- 8 References
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.[2]
It is not as good as either metformin or insulin in those who have gestational diabetes.[3]
Side effects and contraindications
This drug is a major cause of drug-induced hypoglycemia. The risk is greater than with other sulfonylureas.[4] Cholestatic jaundice is noted.
Glibenclamide may be not recommended in those with G6PD deficiency, as it may cause acute haemolysis.[5]
Mechanism of action
The drug works by binding to and inhibiting the ATP-sensitive potassium channels (KATP) inhibitory regulatory subunit sulfonylurea receptor 1 (SUR1) [6] 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.[7] Moreover, under ischemic conditions SUR1, the regulatory subunit of the KATP- and the NCCa-ATP-channels, is expressed in neurons, astrocytes, oligodendrocytes, endothelial cells[8] and by reactive microglia.[7]
Analogs
Additional glibenclamide structural analogs have been prepared by Ahmadi et al.[9]
Research
Glibenclamide improves outcome in animal stroke models by preventing brain swelling[10] and enhancing neuroprotection.[6] 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.[11]
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
- ^ Marble A (1971). "Glibenclamide, a new sulphonylurea: whither oral hypoglycaemic agents?". Drugs. 1 (2): 109–15. doi:10.2165/00003495-197101020-00001. PMID 4999930.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ a b 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.
- ^ a b 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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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Oral anti-diabetic drugs, insulins and insulin analogs, and other drugs used in diabetes (A10)
|
| Insulin |
| Sensitizers |
| Biguanides |
- Buformin‡
- Metformin#
- Phenformin‡
|
| TZDs/"glitazones" (PPAR) |
- Ciglitazone§
- Darglitazone§
- Englitazone§
- Lobeglitazone
- Netoglitazone§
- Pioglitazone
- Rivoglitazone†
- Rosiglitazone
- Troglitazone‡
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| Dual PPAR agonists |
- Aleglitazar†
- Muraglitazar§
- Saroglitazar
- Tesaglitazar§
|
|
| Secretagogues |
| K+ATP |
| Sulfonylureas |
- 1st generation: Acetohexamide
- Carbutamide
- Chlorpropamide
- Glycyclamide
- Metahexamide
- Tolazamide
- Tolbutamide
- 2nd generation: Glibenclamide (glyburide)
- Glibornuride
- Glicaramide
- Gliclazide#
- Glimepiride
- Glipizide
- Gliquidone
- Glisoxepide
- Glyclopyramide
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| Meglitinides/"glinides" |
- Mitiglinide
- Nateglinide
- Repaglinide
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|
| GLP-1 agonists |
- Albiglutide
- Dulaglutide
- Exenatide
- Liraglutide
- Lixisenatide
- Semaglutide†
- Taspoglutide†
|
| DPP-4 inhibitors/"gliptins" |
- Alogliptin
- Anagliptin
- Evogliptin
- Garvagliptin
- Gemigliptin
- Linagliptin
- Melogliptin
- Omarigliptin
- Saxagliptin
- Sitagliptin
- Teneligliptin
- Trelagliptin
- Vildagliptin
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| Free fatty acid receptor 1 (GPR40) |
|
|
| Analogs/other insulins |
- fast-acting (Insulin aspart
- Insulin glulisine
- Insulin lispro)
- short-acting (Regular insulin)
- long-acting (Insulin detemir
- Insulin glargine
- NPH insulin)
- ultra-long-acting (Insulin degludec)
- inhalable (Exubera‡
- Afrezza)
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|
| Other |
| Aldose reductase inhibitors |
- Epalrestat
- Fidarestat§
- Ranirestat†
- Tolrestat‡
- Zenarestat§
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| Alpha-glucosidase inhibitors |
- Acarbose
- Miglitol
- Voglibose
|
| Amylin analog |
|
| Sodium glucose transporter (SGLT2) inhibitors/"gliflozins" |
- Canagliflozin
- Dapagliflozin
- Empagliflozin
- Ipragliflozin
- Remogliflozin§
- Sergliflozin§
- Tofogliflozin†
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| Other |
- Benfluorex‡
- Bromocriptine
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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Ion channel modulators
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| Calcium |
| VDCCs |
| Blockers |
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| Activators |
- L-type-selective: Bay K8644
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| Potassium |
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| Sodium |
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| Chloride |
| CaCCs |
| Blockers |
- Crofelemer
- DIDS
- Ethacrynic acid
- Flufenamic acid
- Fluoxetine
- Furosemide
- Glibenclamide
- Mefloquine
- Mibefradil
- Niflumic acid
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| Activators |
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| CFTR |
| Blockers |
- Glibenclamide
- Lonidamine
- Piretanide
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| Activators |
- 1,7-Phenanthroline
- 1,10-Phenanthroline
- 4,7-Phenanthroline
- 7,8-Benzoquinoline
- Ivacaftor
- Phenanthridine
|
|
| Unsorted |
| Blockers |
- Bumetanide
- Flufenamic acid
- Meclofenamic acid
- Mefenamic acid
- Mepacrine
- Niflumic acid
- Talniflumate
- Tolfenamic acid
- Trifluoperazine
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| Others |
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See also: Receptor/signaling modulators • Transient receptor potential channel modulators
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