U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C23H28ClN3O5S
Molecular Weight 494.0054
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GLYBURIDE

SMILES

COc1ccc(cc1C(=NCCc2ccc(cc2)S(=O)(=O)NC(=NC3CCCCC3)O)O)Cl

InChI

InChIKey=ZNNLBTZKUZBEKO-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C23H28ClN3O5S
Molecular Weight 494.0054
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/017532Orig1s034lbl.pdf

Glyburide, a second-generation sulfonylurea antidiabetic agent, lowers blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. With chronic administration in Type II diabetic patients, the blood glucose lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may be involved in the mechanism of action of oral sulfonyl-urea hypoglycemic drugs. The combination of glibenclamide and metformin may have a synergistic effect, since both agents act to improve glucose tolerance by different but complementary mechanisms. In addition to its blood glucose lowering actions, glyburide produces a mild diuresis by enhancement of renal free water clearance. Glyburide is twice as potent as the related second-generation agent glipizide. Sulfonylureas such as glyburide bind to ATP-sensitive potassium channels on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin. Glyburide is indicated as an adjunct to diet to lower the blood glucose in patients with NIDDM whose hyperglycemia cannot be satisfactorily controlled by diet alone. Glyburide 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.

CNS Activity

Curator's Comment:: Weak penetration in rodents was shown. Glyburide reaches the central nervous system when given systemically, is rapidly removed across the BBB when given intracranioventricularly, and any Glyburide that does enter (and is below detection limit) is insufficient to influence neuronal function

Originator

Sources: Pharmaceutical Manufacturing Encyclopedia retrieved from William Andrew Publishing, p.1783
Curator's Comment:: Introduced as Daonil by Hoechst, Germany

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Diaßeta

Approved Use

Diaßeta is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Launch Date

4.52131193E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
91.1 ng/mL
1.75 mg single, oral
dose: 1.75 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GLYBURIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
323.9 ng × h/mL
1.75 mg single, oral
dose: 1.75 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GLYBURIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2 h
1.75 mg single, oral
dose: 1.75 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GLYBURIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
40 mg 1 times / day multiple, oral
Highest studied dose
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, adult
n = 23
Health Status: unhealthy
Condition: diabetes
Age Group: adult
Sex: M+F
Population Size: 23
Sources:
5 mg 1 times / day multiple, oral (median)
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Sources:
unhealthy, mean age 32.8 years
n = 236
Health Status: unhealthy
Condition: gestational diabetes mellitus
Age Group: mean age 32.8 years
Sex: F
Population Size: 236
Sources:
Disc. AE: Hypoglycemia...
AEs leading to
discontinuation/dose reduction:
Hypoglycemia (5%)
Sources:
2.5 mg 1 times / day steady, oral (starting)
Dose: 2.5 mg, 1 times / day
Route: oral
Route: steady
Dose: 2.5 mg, 1 times / day
Sources:
unhealthy|pregnant
n = 189
Health Status: unhealthy|pregnant
Condition: Mild Gestational Diabetes
Sex: F
Population Size: 189
Sources:
Other AEs: Facial swelling...
Other AEs:
Facial swelling (serious, 1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Hypoglycemia 5%
Disc. AE
5 mg 1 times / day multiple, oral (median)
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Sources:
unhealthy, mean age 32.8 years
n = 236
Health Status: unhealthy
Condition: gestational diabetes mellitus
Age Group: mean age 32.8 years
Sex: F
Population Size: 236
Sources:
Facial swelling serious, 1 patient
2.5 mg 1 times / day steady, oral (starting)
Dose: 2.5 mg, 1 times / day
Route: oral
Route: steady
Dose: 2.5 mg, 1 times / day
Sources:
unhealthy|pregnant
n = 189
Health Status: unhealthy|pregnant
Condition: Mild Gestational Diabetes
Sex: F
Population Size: 189
Sources:
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
weak [IC50 90 uM]
weak (co-administration study)
Comment: Glyburide reduced the mean AUCτ of bosentan and the phenol, hydroxy, and hydroxy-phenol metabolites 29%, 26%, 25%, and 22% (all P < .05), respectively
Page: 2.0
yes [IC50 11.3 uM]
weak (co-administration study)
Comment: Glyburide reduced the mean AUCτ of bosentan and the phenol, hydroxy, and hydroxy-phenol metabolites 29%, 26%, 25%, and 22% (all P < .05), respectively
Page: 2.0
yes [IC50 15 uM]
yes [IC50 18.8 uM]
yes [IC50 199 uM]
yes [Ki 0.75 uM]
Drug as victim
PubMed

PubMed

TitleDatePubMed
Glibenclamide induced chronic cholestasis simulating primary biliary cirrhosis: a case report.
1996 Mar
Glyburide-ciprofloxacin interaction with resistant hypoglycemia.
2000 Aug
Diflubenzuron, a benzoyl-urea insecticide, is a potent inhibitor of TCDD-induced CYP1A1 expression in HepG2 cells.
2000 May 1
Drug interaction: omeprazole and phenprocoumon.
2001
Role of pertussis toxin-sensitive G-proteins in intracellular Ca2+ release and apoptosis induced by inhibiting cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels in HepG2 human hepatoblastoma cells.
2001
The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions.
2001 Apr
Levosimendan increases diastolic coronary flow in isolated guinea-pig heart by opening ATP-sensitive potassium channels.
2001 Apr
Effects of bezafibrate on insulin sensitivity and insulin secretion in non-obese Japanese type 2 diabetic patients.
2001 Apr
Troglitazone prevents the rise in visceral adiposity and improves fatty liver associated with sulfonylurea therapy--a randomized controlled trial.
2001 Apr
Protein kinase C isoform-dependent modulation of ATP-sensitive K+ channels during reoxygenation in guinea-pig ventricular myocytes.
2001 Apr 1
Flow-induced dilation of human coronary arterioles: important role of Ca(2+)-activated K(+) channels.
2001 Apr 17
Effects of phosphodiesterase inhibitors on hypoxic pulmonary vasoconstriction. Influence of K(+) channels and nitric oxide.
2001 Apr 6
Changes in cell volume induced by activation of the cyclic amp-dependent chloride channel in guinea-pig cardiac myocytes.
2001 Feb
The sulphonylurea glibenclamide inhibits multidrug resistance protein (MRP1) activity in human lung cancer cells.
2001 Feb
K(ATP)(+) channels, nitric oxide, and adenosine are not required for local metabolic coronary vasodilation.
2001 Feb
Protein kinase C and G(i/o) proteins are involved in adenosine- and ischemic preconditioning-mediated renal protection.
2001 Feb
Altered effects of potassium channel modulation in the coronary circulation in experimental hypercholesterolemia.
2001 Feb 1
Potassium ions as vasodilators: role of inward rectifier potassium channels.
2001 Feb 2
[Gestational diabetes: an alternative to insulin therapy?].
2001 Feb 3
Effect of glibenclamide in gabapentin antinociception.
2001 Jan
Verapamil prevents stretch-induced shortening of atrial effective refractory period in langendorff-perfused rabbit heart.
2001 Jan
Experimental leishmaniasis: synergistic effect of ion channel blockers and interferon-gamma on the clearance of Leishmania major by macrophages.
2001 Jan
Near-normoglycaemic remission in African-Americans with Type 2 diabetes mellitus is associated with recovery of beta cell function.
2001 Jan
Three types of K(+) currents in murine osteocyte-like cells (MLO-Y4).
2001 Jan
In vivo evidence for K(Ca) channel opening properties of acetazolamide in the human vasculature.
2001 Jan
Involvement of Ca2+ -activated K+ channels in ginsenosides-induced aortic relaxation in rats.
2001 Jan
Adenosine A1 receptor activation reduces reactive oxygen species and attenuates stunning in ventricular myocytes.
2001 Jan
Cause of high variability in drug dissolution testing and its impact on setting tolerances.
2001 Jan
Intrahippocampal infusions of k-atp channel modulators influence spontaneous alternation performance: relationships to acetylcholine release in the hippocampus.
2001 Jan 15
ATP-binding cassette transporter A1 (ABCA1) functions as a cholesterol efflux regulatory protein.
2001 Jun 29
Hypoglycemic and antihyperglycemic activity of Syzygium alternifolium (Wt.) Walp. seed extracts in normal and diabetic rats.
2001 Mar
Hemodynamic, metabolic and hormonal responses to oral glibenclamide in patients with cirrhosis receiving glucose.
2001 Mar
The role of K+ATP channels in the control of pre- and post-ischemic left ventricular developed pressure in septic rat hearts.
2001 Mar
Improvement of glycemic control by 1 year of insulin therapy leads to a sustained decrease in sE-selectin concentrations in type 2 diabetes.
2001 Mar
Inhibitory effects of nicorandil on rat mesangial cell proliferation via the protein kinase G pathway.
2001 Mar
HNS-32, a novel azulene-1-carboxamidine derivative, inhibits nifedipine-sensitive and -insensitive contraction of the isolated rabbit aorta.
2001 Mar
Effect of Aloe vera leaves on blood glucose level in type I and type II diabetic rat models.
2001 Mar
The mechanism of gentisic acid-induced relaxation of the guinea pig isolated trachea: the role of potassium channels and vasoactive intestinal peptide receptors.
2001 Mar
Mechanism of CGRP-induced relaxation in rat intramural coronary arteries.
2001 Mar
Functional characterisation of human TASK-3, an acid-sensitive two-pore domain potassium channel.
2001 Mar
Characterization of secretory and morphologic properties of primary cultured endocrine cells from porcine pancreata.
2001 Mar
Concentration of the complement activation product, acylation-stimulating protein, is related to C-reactive protein in patients with type 2 diabetes.
2001 Mar
Multiple Ca(2+)-dependent modulators mediate alkalosis-induced vasodilation in newborn piglet lungs.
2001 Mar
Regulation of an outwardly rectifying chloride conductance in renal epithelial cells by external and internal calcium.
2001 Mar 1
Gramicidin-perforated patch analysis on HCO3- secretion through a forskolin-activated anion channel in rat parotid intralobular duct cells.
2001 Mar 1
Nicorandil--induced ATP release in endothelial cells of rat caudal artery is associated with increase in intracellular Ca(2+).
2001 Mar 30
Functional roles of cardiac and vascular ATP-sensitive potassium channels clarified by Kir6.2-knockout mice.
2001 Mar 30
Characteristics of pancreatic beta-cell secretion in Type 2 diabetic patients treated with gliclazide and glibenclamide.
2001 May
Diamidine compounds: selective uptake and targeting in Plasmodium falciparum.
2001 May
Phospholipids as modulators of K(ATP) channels: distinct mechanisms for control of sensitivity to sulphonylureas, K(+) channel openers, and ATP.
2001 May
Patents

Sample Use Guides

The usual starting dose is 2.5 to 5 mg daily, administered with breakfast or the first main meal. Those patients who may be more sensitive to hypoglycemic drugs should be started at 1.25 mg daily. The usual maintenance dose is in the range of 1.25 to 20 mg daily, which may be given as a single dose or in divided doses.
Route of Administration: Oral
Inhibition of ABCA1 by glibenclamide (Glyburide) has been reported to occur in the concentration range of 100 to 1,000 uM
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:00:37 UTC 2021
Edited
by admin
on Fri Jun 25 21:00:37 UTC 2021
Record UNII
SX6K58TVWC
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
GLYBURIDE
MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-IP  
USAN  
Official Name English
U-26452
Code English
CIRARA
Brand Name English
HB-419
Code English
GLIBENCLAMIDE [EP MONOGRAPH]
Common Name English
GLYBURIDE [WHO-IP]
Common Name English
GLYBURIDE [MI]
Common Name English
GLYBENCLAMIDE
Common Name English
U-26,45
Code English
GLYBURIDE [USP MONOGRAPH]
Common Name English
GLUCOVANCE COMPONENT GLYBURIDE
Common Name English
GLYBURIDE COMPONENT OF GLUCOVANCE
Common Name English
MICRONASE
Brand Name English
HB 419
Code English
GLYBURIDE [USAN]
Common Name English
NSC-759618
Code English
GLIBENCLAMIDUM [WHO-IP LATIN]
Common Name English
GLIBENCLAMIDE
EP   INN   MART.   WHO-DD   WHO-IP  
INN  
Official Name English
GLYBURIDE [VANDF]
Common Name English
BENZAMIDE, 5-CHLORO-N-(2-(4-((((CYCLOHEXYLAMINO)CARBONYL)AMINO)SULFONYL)PHENYL)ETHYL)-2-METHOXY-
Systematic Name English
GLIBENCLAMIDE [MART.]
Common Name English
GLIBENCLAMIDE [WHO-IP]
Common Name English
U-26,452
Code English
GLIBENCLAMIDE [WHO-DD]
Common Name English
GLYBURIDE [USP-RS]
Common Name English
GLIBENCLAMIDE [INN]
Common Name English
GLYNASE
Brand Name English
DIABETA
Brand Name English
1-((P-(2-(5-CHLORO-O-ANISAMIDO)ETHYL)PHENYL)SULFONYL)-3-CYCLOHEXYLUREA
Common Name English
GLYBURIDE [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
NDF-RT N0000008054
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
NDF-RT N0000008054
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
FDA ORPHAN DRUG 502615
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
FDA ORPHAN DRUG 518816
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
LIVERTOX 463
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
WHO-VATC QA10BB01
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
NDF-RT N0000175608
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
FDA ORPHAN DRUG 539316
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
NDF-RT N0000008054
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
FDA ORPHAN DRUG 491215
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 18.5
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
EU-Orphan Drug EU/3/15/1589
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
NCI_THESAURUS C97936
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
WHO-ATC A10BB01
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
Code System Code Type Description
EVMPD
SUB07916MIG
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
INN
2386
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
GLYBURIDE
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY Description: A white or almost white, crystalline powder; odourless or almost odourless. Solubility: Practically insoluble in water and ether R; slightly soluble in ethanol (~750 g/l) TS and methanol R. Category: Antidiabetic agent. Storage: Glibenclamide should be kept in a well-closed container. Definition: Glibenclamide contains not less than 98.5% and not more than 101.0% of C23H28ClN3O5S, calculated with reference to the dried substance.
DRUG CENTRAL
1314
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
MERCK INDEX
M5784
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY Merck Index
USP_CATALOG
1295505
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY USP-RS
LACTMED
Glyburide
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
PUBCHEM
3488
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
CAS
10238-21-8
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
FDA UNII
SX6K58TVWC
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
ECHA (EC/EINECS)
233-570-6
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
MESH
D005905
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
IUPHAR
2414
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
WIKIPEDIA
GLIBENCLAMIDE
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
DRUG BANK
DB01016
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
RXCUI
4815
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY RxNorm
EPA CompTox
10238-21-8
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
NCI_THESAURUS
C29076
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
ChEMBL
CHEMBL472
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
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