View source for Glibenclamide

{{distinguish|gliclazide|glipizide}}
{{drugbox
| verifiedrevid = 297783872
| IUPAC_name = 5-chloro-''N''-(4-[''N''-(cyclohexylcarbamoyl)sulfamoyl]phenethyl)-2-methoxybenzamide
| image = Glibenclamide.svg
| image2 = Glibenclamide 3D.png
| CASNo_Ref = {{cascite}}
| CAS_number = 10238-21-8
| ChemSpiderID = 3368
| ATC_prefix = A10
| ATC_suffix = BB01 
| PubChem = 3488
| IUPHAR_ligand = 2414
| DrugBank = APRD00233
| C = 23 |H = 28 |Cl = 1 |N = 3 |O = 5 |S = 1
| molecular_weight = 494.004 [[Gram|g]]/[[Mole (unit)|mol]]
| bioavailability = 
| protein_bound = Extensive
| metabolism = [[Liver|Hepatic]] [[hydroxylation]] ([[CYP2C9]]-mediated)
| elimination_half-life = 10 [[hour]]s
| excretion = [[Kidney|Renal]] and biliary
| licence_US = Glyburide
| pregnancy_AU = C
| pregnancy_US = B
| legal_UK = POM
| legal_US = Rx-only
| routes_of_administration = Oral
}}
'''Glibenclamide''' ([[International Nonproprietary Name|INN]]), also known as '''glyburide''' ([[United States Adopted Name|USAN]]), is an [[anti-diabetic drug]] in a class of medications known as [[sulfonylurea]]s, 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).<ref>{{Cite journal
|inventor-last=Matsui
|inventor-first=Rakan
|inventor2-last=Kiyota
|inventor2-first=Yuko
|inventor3-last=Nakashima
|inventor3-first=Masaya
|inventor4-last=Kanayama
|inventor4-first=Toshiji
|title=Transdermal composition containing glibenclamide and benzyl alcohol
|issue-date=3 May 2003 
|patent-number=0976406
|country-code=EP}}</ref>

It is sold in doses of 1.25&nbsp;mg, 2.5&nbsp;mg and 5&nbsp;mg, under the trade names '''Diabeta''', '''Glynase''' and '''Micronase''' in the [[United States]] and '''Daonil''', '''Semi-Daonil''' and '''Euglucon''' in the [[United Kingdom]].

It is also sold in combination with [[metformin]] under the trade names '''Glucovance''' and '''Glibomet'''.

==Uses==
It is used in the treatment of [[type II diabetes]]. {{As of|2007}}, it is one of only two oral anti-diabetics in the [[World Health Organization Model List of Essential Medicines]] (the other being [[metformin]]).<ref>(March 2007) {{PDFlink|
[http://www.who.int/medicines/publications/EML15.pdf ''WHO Model List of Essential Medicines'']|612&nbsp;[[Kibibyte|KiB]]<!-- application/pdf, 626969 bytes -->}}, 15<sup>th</sup> edition, [[World Health Organization]], p. 21. Retrieved on 2007-11-19.</ref> As of 2003, in the United States, it was the most popular sulfonylurea.<ref name="pmid12574174">{{cite journal |author=Riddle MC |title=Editorial: sulfonylureas differ in effects on ischemic preconditioning--is it time to retire glyburide? |journal=J. Clin. Endocrinol. Metab. |volume=88 |issue=2 |pages=528–30 |year=2003 |month=February |pmid=12574174 |doi= 10.1210/jc.2002-021971|url=http://jcem.endojournals.org/cgi/pmidlookup?view=long&pmid=12574174}}</ref>

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.

==Mechanism of action==
The drug works by inhibiting [[ATP-sensitive potassium channel]]s<ref name="pmid17015627">{{cite journal |author=Serrano-Martín X, Payares G, Mendoza-León A |title=Glibenclamide, a blocker of K+(ATP) channels, shows antileishmanial activity in experimental murine cutaneous leishmaniasis |journal=Antimicrob. Agents Chemother. |volume=50 |issue=12 |pages=4214–6 |year=2006 |month=December |pmid=17015627 |pmc=1693980 |doi=10.1128/AAC.00617-06 |url=http://aac.asm.org/cgi/pmidlookup?view=long&pmid=17015627}}</ref> in [[pancreas|pancreatic]] [[beta cell]]s. This inhibition causes cell membrane depolarization, which causes [[voltage-dependent calcium channel]]s to open, which causes an increase in intracellular [[calcium]] in the [[beta cell]], which stimulates [[insulin]] release.

==Side effects and contraindications==
This drug is a major cause of drug induced [[hypoglycemia]]. Cholestatic jaundice is noted.

Recently published data suggests that 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.<ref>{{cite journal | author = Monami M, Luzzi C, Lamanna C, Chiasserini V, Addante F, Desideri CM, Masotti G, Marchionni N, Mannucci E | title = Three-year mortality in diabetic patients treated with different combinations of insulin secretagogues and metformin | journal = Diabetes Metab Res Rev | volume = 22 | issue = 6 | pages = 477–82 | year = 2006 | pmid = 16634115 | doi = 10.1002/dmrr.642 }}</ref>

==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.

[[File:Glibenclamide synth.png|600px]]

{{Cite journal|doi=10.1002/jlcr.2590090112|title=Synthesis of carbon-14 and tritium labeled glyburide|year=1973|last1=Hsi|first1=R. S. P.|journal=Journal of Labelled Compounds|volume=9|pages=91}}

==References==
{{Reflist}}

{{Oral hypoglycemics}}

[[Category:Sulfonylureas]]
[[Category:World Health Organization essential medicines]]
[[Category:Organochlorides]]
[[Category:Phenol ethers]]
[[Category:Benzamides]]


{{pharma-stub}}

[[de:Glibenclamid]]
[[es:Glibenclamida]]
[[fa:گلی‌بن‌ کلامید]]
[[it:Glibenclamide]]
[[pl:Glibenklamid]]
[[zh:格列苯脲]]
[[Category:2Fix]]