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Identification
Name Glimepiride
Accession Number DB00222 (APRD00381)
Type small molecule
Groups approved
Description

Glimepiride is the first III generation sulphonyl urea it is a very potent sulphonyl urea with long duration of action.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Glimepirid
  • Glimepirida
  • Glimepiridum
  • Glimepride
Brand names
  • Amarel
  • Amaryl
  • Endial
  • Novo-glimepiride
  • PMS-glimepiride
  • Ratio-glimepiride
  • Sandoz glimepiride
Brand name mixtures
  • Avandaryl (glimepiride + rosiglitazone maleate)
Categories
  • Hypoglycemic Agents
  • Antiarrhythmic Agents
  • Immunosuppressive Agents
  • Sulfonylureas
  • Anti-Arrhythmia Agents
CAS number 93479-97-1
Weight Average: 490.616
Monoisotopic: 490.224990908
Chemical Formula C24H34N4O5S
InChI Key InChIKey=WIGIZIANZCJQQY-UHFFFAOYSA-N
InChI
InChI=1S/C24H34N4O5S/c1-4-21-17(3)15-28(22(21)29)24(31)25-14-13-18-7-11-20(12-8-18)34(32,33)27-23(30)26-19-9-5-16(2)6-10-19/h7-8,11-12,16,19H,4-6,9-10,13-15H2,1-3H3,(H,25,31)(H2,26,27,30)
Plain Text
IUPAC Name
3-ethyl-4-methyl-N-{2-[4-({[(4-methylcyclohexyl)carbamoyl]amino}sulfonyl)phenyl]ethyl}-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamide
SMILES
CCC1=C(C)CN(C(=O)NCCC2=CC=C(C=C2)S(=O)(=O)NC(=O)NC2CCC(C)CC2)C1=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Sulfonylureas
Substructures
  • Sulfonylureas
  • Alkanes and Alkenes
  • Amino Ketones
  • Sulfonyls
  • Benzene and Derivatives
  • Ureas and Derivatives
  • Benzenesulfonamides
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Sulfonamides
  • Carboxylic Acids and Derivatives
  • Pyrrolines
Pharmacology
Indication For concomitant use with insulin for the treatment of noninsulin-dependent (type 2) diabetes mellitus.
Pharmacodynamics Glimepiride, like glyburide and glipizide, is a "second-generation" sulfonylurea agents. Glimepiride is used with diet to lower blood glucose by increasing the secretion of insulin from pancreas and increasing the sensitivity of peripheral tissues to insulin.
Mechanism of action The mechanism of action of glimepiride in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells, and increasing sensitivity of peripheral tissues to insulin. Glimepiride likely binds to ATP-sensitive potassium channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Membrane depolarization stimulates calcium ion influx through voltage-sensitive calcium channels. This increase in intracellular calcium ion concentration induces the secretion of insulin.
Absorption Completely (100%) absorbed following oral administration.
Volume of distribution
  • 21.8 ± 13.9 L [Volunteers]
  • 19.8 ± 12.7 L [Patients with Type 2 diabetes, Single Dose]
  • 37.1 ± 18.2 L [Patients with Type 2 diabetes, Multiple Dose]
Protein binding Over 99.5% bound to plasma protein.
Metabolism

Hepatic. Following either an intravenous or oral dose, glimepiride is completely metabolized by oxidative biotransformation to a major metabolite, cyclohexyl hydroxymethyl derivative (M1), via the hepatic cytochrome P450 II C9 subsystem. M1 is further metabolized to the carboxyl derivative (M2) by one or several cytosolic enzymes. M1, but not M2, possessed approximately one third of the pharmacologic activity of its parent in an animal model. However, whether the glucose-lowering effect of M1 is clinically significant is not clear.
Route of elimination Not Available
Half life Approximately 5 hours following single dose.
Clearance
  • 52.1 +/- 16.0 mL/min [Normal subjects with single oral dose]
  • 48.5 +/- 29.3 mL/min [Patients with Type 2 diabetes, with single oral dose]
  • 52.7 +/- 40.3 mL/min [Patients with Type 2 diabetes, with multiple oral dose]
  • 47.8 mL/min [healthy after intravenous (IV) dosing]
Toxicity Severe hypoglycemic reactions with coma, seizure, or other neurological impairment.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
  • Accord healthcare inc
  • Carlsbad technology inc
  • Corepharma llc
  • Dr reddys laboratories ltd
  • Genpharm inc
  • Invagen pharmaceuticals inc
  • Mylan pharmaceuticals inc
  • Ranbaxy laboratories ltd
  • Teva pharmaceuticals usa inc
  • Vintage pharmaceuticals llc
  • Watson laboratories inc
  • Watson laboratories inc florida
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Amaryl 4 mg tablet 2.11 USD tablet
Amaryl 2 mg tablet 1.25 USD tablet
Glimepiride 4 mg tablet 1.25 USD tablet
Amaryl 1 mg tablet 0.88 USD tablet
Glimepiride 2 mg tablet 0.67 USD tablet
Glimepiride 1 mg tablet 0.42 USD tablet
Patents Not Available
Properties
State solid
Melting point 207 oC
Experimental Properties
Property Value Source
water solubility Insoluble PhysProp
logP 3.5 PhysProp
Predicted Properties
Property Value Source
water solubility 3.84e-02 g/l ALOGPS
logP 2.82 ALOGPS
logP 3.12 ChemAxon Molconvert
logS -4.11 ALOGPS
pKa 14.12 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 3 ChemAxon Molconvert
polar surface area 124.68 ChemAxon Molconvert
rotatable bond count 6 ChemAxon Molconvert
refractivity 129.80 ChemAxon Molconvert
polarizability 53.86 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00593 Link_out
KEGG Compound C07669 Link_out
PubChem Compound 3476 Link_out
PubChem Substance 46508842 Link_out
ChemSpider 3357 Link_out
ChEBI 5383 Link_out
ChEMBL 5383 Link_out
Therapeutic Targets Database DAP000132 Link_out
PharmGKB PA449761 Link_out
Drug Product Database 2245274 Link_out
RxList http://www.rxlist.com/cgi/generic/glimepiride.htm Link_out
Drugs.com http://www.drugs.com/cdi/glimepiride.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Glimepiride Link_out
ATC Codes
  • A10BB12
AHFS Codes
  • 68:20.20
PDB Entries Not Available
FDA label show (176.4 KB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Even though food reduces product absorption, the manufacturer recommends taking the product with the first meal of the day.
Targets

1. ATP-sensitive inward rectifier potassium channel 11

Pharmacological action: yes
Actions: inhibitor

This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium

Organism class: human
UniProt ID: Q14654 Link_out
Gene: KCNJ11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Song DK, Ashcroft FM: Glimepiride block of cloned beta-cell, cardiac and smooth muscle K(ATP) channels. Br J Pharmacol. 2001 May;133(1):193-9. Pubmed
  2. Lawrence CL, Rainbow RD, Davies NW, Standen NB: Effect of metabolic inhibition on glimepiride block of native and cloned cardiac sarcolemmal K(ATP) channels. Br J Pharmacol. 2002 Jul;136(5):746-52. Pubmed
  3. Bataille D: [Molecular mechanisms of insulin secretion]. Diabetes Metab. 2002 Dec;28(6 Suppl):4S7-13. Pubmed

2. ATP-sensitive inward rectifier potassium channel 1

Pharmacological action: yes
Actions: inhibitor

In the kidney, probably plays a major role in potassium homeostasis. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. This channel is activated by internal ATP and can be blocked by external barium

Organism class: human
UniProt ID: P48048 Link_out
Gene: KCNJ1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Proks P, Reimann F, Green N, Gribble F, Ashcroft F: Sulfonylurea stimulation of insulin secretion. Diabetes. 2002 Dec;51 Suppl 3:S368-76. Pubmed
  4. Bataille D: [Molecular mechanisms of insulin secretion]. Diabetes Metab. 2002 Dec;28(6 Suppl):4S7-13. Pubmed

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

Pharmacological action: yes
Actions: inducer

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. Muller G, Hartz D, Punter J, Okonomopulos R, Kramer W: Differential interaction of glimepiride and glibenclamide with the beta-cell sulfonylurea receptor. I. Binding characteristics. Biochim Biophys Acta. 1994 May 11;1191(2):267-77. Pubmed
  2. Kramer W, Muller G, Geisen K: Characterization of the molecular mode of action of the sulfonylurea, glimepiride, at beta-cells. Horm Metab Res. 1996 Sep;28(9):464-8. Pubmed
  3. Kramer W, Muller G, Girbig F, Gutjahr U, Kowalewski S, Hartz D, Summ HD: The molecular interaction of sulfonylureas with beta-cell ATP-sensitive K(+)-channels. Diabetes Res Clin Pract. 1995 Aug;28 Suppl:S67-80. 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. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. 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
  3. 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
Comments
Drug created on June 13, 2005 07:24 / Updated on January 22, 2011 08:58

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.