Banner
Identification
Name Gliclazide
Accession Number DB01120 (APRD00460)
Type small molecule
Groups approved
Description

Gliclazide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It belongs to the sulfonylurea class of insulin secretagogues, which act by stimulating β cells of the pancreas to release insulin. Sulfonylureas increase both basal insulin secretion and meal-stimulated insulin release. Medications in this class differ in their dose, rate of absorption, duration of action, route of elimination and binding site on their target pancreatic β cell receptor. Sulfonylureas also increase peripheral glucose utilization, decrease hepatic gluconeogenesis and may increase the number and sensitivity of insulin receptors. Sulfonylureas are associated with weight gain, though less so than insulin. Due to their mechanism of action, sulfonylureas may cause hypoglycemia and require consistent food intake to decrease this risk. The risk of hypoglycemia is increased in elderly, debilitated and malnourished individuals. Gliclazide has been shown to decrease fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels (reflective of the last 8-10 weeks of glucose control). Gliclazide is extensively metabolized by the liver; its metabolites are excreted in both urine (60-70%) and feces (10-20%).
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
1-(3-Azabicyclo(3.3.0)oct-3-yl)-3-(p-tolylsulfonyl)urea
1-(Hexahydrocyclopenta(c)pyrrol-2(1H)-yl)-3-(p-tolylsulfonyl)urea
Gliclazida [INN-Spanish]
Gliclazidum [INN-Latin]
N-(4-Methylbenzenesulfonyl)-N'-(3-azabicyclo(3.3.0)oct-3-yl)urea
Salts Not Available
Brand names
Name Company
Diamicron Servier
Diamicron MR Servier
Glimicron
Mylan-Gliclazide Mylan
Nordialex
PMS-Gliclazide Pharmascience
Brand mixtures Not Available
Categories
  • Hypoglycemic Agents
  • Sulfonylureas
  • Antidiabetic
CAS number 21187-98-4
Weight Average: 323.411
Monoisotopic: 323.130362243
Chemical Formula C15H21N3O3S
InChI Key InChIKey=BOVGTQGAOIONJV-UHFFFAOYSA-N
InChI
InChI=1S/C15H21N3O3S/c1-11-5-7-14(8-6-11)22(20,21)17-15(19)16-18-9-12-3-2-4-13(12)10-18/h5-8,12-13H,2-4,9-10H2,1H3,(H2,16,17,19)
Plain Text
IUPAC Name
1-[(4-methylbenzene)sulfonyl]-3-{octahydrocyclopenta[c]pyrrol-2-yl}urea
SMILES
CC1=CC=C(C=C1)S(=O)(=O)NC(=O)NN1CC2CCCC2C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Sulfonylureas
Substructures
  • Sulfonylureas
  • Sulfonyls
  • Pyrrolidines
  • Benzene and Derivatives
  • Benzenesulfonamides
  • Heterocyclic compounds
  • Aromatic compounds
  • Sulfonamides
  • Semicarbazides
  • Hydrazine Derivatives
Pharmacology
Indication For the treatment of NIDDM in conjunction with diet and exercise.
Pharmacodynamics Gliclazide is a second generation sulphonylurea which acts as a hypoglycemic agent. It stimulates β cells of the islet of Langerhans in the pancreas to release insulin. It also enhances peripheral insulin sensitivity. Overall, it potentiates insulin release and improves insulin dynamics.
Mechanism of action Gliclazide binds to the β cell sulfonyl urea receptor (SUR1). This binding subsequently blocks the ATP sensitive potassium channels. The binding results in closure of the channels and leads to a resulting decrease in potassium efflux leads to depolarization of the β cells. This opens voltage-dependent calcium channels in the β cell resulting in calmodulin activation, which in turn leads to exocytosis of insulin containing secretorty granules.
Absorption Rapidly and well absorbed but may have wide inter- and intra-individual variability. Peak plasma concentrations occur within 4-6 hours of oral administration.
Volume of distribution Not Available
Protein binding 94%, highly bound to plasma proteins
Metabolism Extensively metabolized in the liver. Less than 1% of the orally administered dose appears unchanged in the urine. Metabolites include oxidized and hydroxylated derivates, as well as glucuronic acid conjugates.
Route of elimination Metabolites and conjugates are eliminated primarily by the kidneys (60-70%) and also in the feces (10-20%).
Half life 10.4 hours. Duration of action is 10-24 hours.
Clearance Not Available
Toxicity LD50=3000 mg/kg (orally in mice). Gliclazide and its metabolites may accumulate in those with severe hepatic and/or renal dysfunction. Symptoms of hypoglycemia include: dizziness, lack of energy, drowsiness, headache and sweating.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00461 Gliclazide Pathway SMP00461
Pharmacoeconomics
Manufacturers
Packagers Not Available
Dosage forms
Form Route Strength
Tablet Oral 80 mg
Tablet, extended release Oral 30 mg
Tablet, extended release Oral 60 mg
Prices
Unit description Cost Unit
Diamicron 80 mg Tablet 0.42 USD tablet
Apo-Gliclazide 80 mg Tablet 0.23 USD tablet
Gliclazide 80 mg Tablet 0.23 USD tablet
Mylan-Gliclazide 80 mg Tablet 0.23 USD tablet
Novo-Gliclazide 80 mg Tablet 0.23 USD tablet
Pms-Gliclazide 80 mg Tablet 0.23 USD tablet
Diamicron Mr 30 mg Sustained-Release Tablet 0.16 USD tablet
Apo-Gliclazide Mr 30 mg Sustained-Release Tablet 0.15 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
Canada 2273420 2002-07-09 2019-05-27
Properties
State solid
Experimental Properties
Property Value Source
melting point 181 °C PhysProp
logP 2.6 Not Available
Predicted Properties
Property Value Source
water solubility 1.90e-01 g/l ALOGPS
logP 1.52 ALOGPS
logP 1.73 ChemAxon
logS -3.2 ALOGPS
pKa (strongest acidic) 4.07 ChemAxon
pKa (strongest basic) 1.38 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 78.51 ChemAxon
rotatable bond count 2 ChemAxon
refractivity 83.88 ChemAxon
polarizability 34.22 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D01599 Link_out
PubChem Compound 3475 Link_out
PubChem Substance 46505475 Link_out
ChemSpider 3356 Link_out
ChEBI 31654 Link_out
ChEMBL 31654 Link_out
Therapeutic Targets Database DAP000522 Link_out
PharmGKB PA10892 Link_out
Drug Product Database 2248453 Link_out
Wikipedia http://en.wikipedia.org/wiki/Gliclazide Link_out
ATC Codes
  • A10BB09
AHFS Codes
  • 68:20.20
PDB Entries Not Available
FDA label Not Available
MSDS show (57.5 KB)
Interactions
Drug Interactions
Drug Interaction
Acebutolol Acebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.
Acetylsalicylic acid Acetylsalicylic acid increases the effect of the sulfonylurea, gliclazide.
Atenolol The beta-blocker, atenolol, may decrease symptoms of hypoglycemia.
Betaxolol The beta-blocker, betaxolol, may decrease symptoms of hypoglycemia.
Bevantolol The beta-blocker, bevantolol, may decrease symptoms of hypoglycemia.
Bismuth Subsalicylate The salicylate, bismuth subsalicylate, increases the effect of the sulfonylurea, gliclazide.
Bisoprolol The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.
Carteolol The beta-blocker, carteolol, may decrease symptoms of hypoglycemia.
Carvedilol The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Chloramphenicol Chloramphenicol may increase the effect of sulfonylurea, gliclazide.
Clofibrate Clofibrate may increase the effect of sulfonylurea, gliclazide.
Dicumarol Dicumarol may increase the effect of sulfonylurea, gliclazide.
Esmolol The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.
Glucosamine Possible hyperglycemia
Labetalol The beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
Magnesium salicylate The salicylate, magnesium salicylate, increases the effect of the sulfonylurea, gliclazide.
Metoprolol The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
Nadolol The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.
Oxprenolol The beta-blocker, oxprenolol, may decrease symptoms of hypoglycemia.
Penbutolol The beta-blocker, penbutolol, may decrease symptoms of hypoglycemia.
Phenylbutazone Phenylbutazone increases the effect of the hypoglycemic agent
Pindolol The beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
Practolol The beta-blocker, practolol, may decrease symptoms of hypoglycemia.
Propranolol The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.
Rifampin Rifampin may decrease the effect of sulfonylurea, gliclazide.
Salicylate-sodium The salicylate, salicylate-sodium, increases the effect of the sulfonylurea, gliclazide.
Salsalate The salicylate, salsalate, increases the effect of the sulfonylurea, gliclazide.
Somatropin recombinant Somatropin may antagonize the hypoglycemic effect of gliclazide. Monitor for changes in fasting and postprandial blood sugars.
Sotalol The beta-blocker, sotalol, may decrease symptoms of hypoglycemia.
Timolol The beta-blocker, timolol, may decrease symptoms of hypoglycemia.
Trisalicylate-choline The salicylate, trisalicylate-choline, increases the effect of the sulfonylurea, gliclazide.
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals. A consistent diet is recommended to reduce the risk of hypoglycemia.
Targets

1. ATP-binding cassette transporter sub-family C member 8

Pharmacological action: yes
Actions: binder

Putative subunit of the beta-cell ATP-sensitive potassium channel (KATP). Regulator of ATP-sensitive K+ channels and insulin release

Organism class: human
UniProt ID: Q09428 Link_out
Gene: ABCC8 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Gribble FM, Ashcroft FM: Sulfonylurea sensitivity of adenosine triphosphate-sensitive potassium channels from beta cells and extrapancreatic tissues. Metabolism. 2000 Oct;49(10 Suppl 2):3-6. Pubmed
  2. Harrower A: Gliclazide modified release: from once-daily administration to 24-hour blood glucose control. Metabolism. 2000 Oct;49(10 Suppl 2):7-11. Pubmed
  3. Lawrence CL, Proks P, Rodrigo GC, Jones P, Hayabuchi Y, Standen NB, Ashcroft FM: Gliclazide produces high-affinity block of KATP channels in mouse isolated pancreatic beta cells but not rat heart or arterial smooth muscle cells. Diabetologia. 2001 Aug;44(8):1019-25. Pubmed
  4. Reimann F, Ashcroft FM, Gribble FM: Structural basis for the interference between nicorandil and sulfonylurea action. Diabetes. 2001 Oct;50(10):2253-9. Pubmed
  5. Proks P, Reimann F, Green N, Gribble F, Ashcroft F: Sulfonylurea stimulation of insulin secretion. Diabetes. 2002 Dec;51 Suppl 3:S368-76. Pubmed

2. Vascular endothelial growth factor A

Pharmacological action: unknown
Actions: other/unknown

Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis, and induces permeabilization of blood vessels. Binds to the VEGFR1/Flt-1 and VEGFR2/Kdr receptors, heparan sulfate and heparin. Neuropilin-1 binds isoforms VEGF-165 and VEGF-145

Organism class: human
UniProt ID: P15692 Link_out
Gene: VEGF Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mamputu JC, Renier G: Advanced glycation end products increase, through a protein kinase C-dependent pathway, vascular endothelial growth factor expression in retinal endothelial cells. Inhibitory effect of gliclazide. J Diabetes Complications. 2002 Jul-Aug;16(4):284-93. Pubmed
  2. Mamputu JC, Renier G: Signalling pathways involved in retinal endothelial cell proliferation induced by advanced glycation end products: inhibitory effect of gliclazide. Diabetes Obes Metab. 2004 Mar;6(2):95-103. Pubmed
  3. Li L, Renier G: Activation of nicotinamide adenine dinucleotide phosphate (reduced form) oxidase by advanced glycation end products links oxidative stress to altered retinal vascular endothelial growth factor expression. Metabolism. 2006 Nov;55(11):1516-23. Pubmed
  4. Kimura T, Takagi H, Suzuma K, Kita M, Watanabe D, Yoshimura N: Comparisons between the beneficial effects of different sulphonylurea treatments on ischemia-induced retinal neovascularization. Free Radic Biol Med. 2007 Aug 1;43(3):454-61. Epub 2007 May 3. Pubmed
Enzymes

1. Cytochrome P450 2C9

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

2. Cytochrome P450 2C19

Actions: substrate, inhibitor

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Carriers

1. Serum albumin

Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood

UniProt ID: P02768 Link_out
Gene: ALB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Igaki A, Kobayashi K, Kimura M, Sakoguchi T, Matsuoka A: Influence of blood proteins on biomedical analysis. XII. Effects of glycation on gliclazide (oral hypoglycemic drug)-binding with serum albumin in diabetics. Chem Pharm Bull (Tokyo). 1992 Jan;40(1):255-7. Pubmed
  2. Kobayashi K, Kimura M, Sakoguchi T, Hase A, Matsuoka A: Influence of blood proteins on biomedical analysis. V. Effect of ethyl alcohol on gliclazide-binding with bovine serum albumin. Chem Pharm Bull (Tokyo). 1982 Mar;30(3):1077-80. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19