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Showing drug card for Glimepiride (DB00222)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:03:41
Primary Accession Number DB00222
Secondary Accession Number
  • APRD00381
Name Glimepiride
Drug Type
  • Approved
  • Small Molecule
Description Glimepiride is the first III generation sulphonyl urea it is a very potent sulphonyl urea with long duration of action.
Synonyms
  1. Glimepirid
  2. Glimepirida
  3. Glimepiridum
  4. Glimepride
Brand Names
  1. Amarel
  2. Amaryl
  3. Endial
  4. Novo-glimepiride
  5. PMS-glimepiride
  6. Ratio-glimepiride
  7. Sandoz glimepiride
Brand Mixtures
  1. Avandaryl (glimepiride + rosiglitazone maleate)
Chemical IUPAC Name 3-ethyl-4-methyl-N-[2-[4-[(4-methylcyclohexyl)carbamoylsulfamoyl]phenyl]ethyl]-2-oxo-5H-pyrrole-1-carboxamide
Chemical Formula C24H34N4O5S
Chemical Structure Structure
CAS Registry Number 93479-97-1
InChI Identifier InChI=1/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)/f/h25-27H
InChI Key WIGIZIANZCJQQY-PLJOYGPPCG
KEGG Drug D00593 Link Image
KEGG Compound C07669 Link Image
PubChem Compound 3476 Link Image
PubChem Substance 193913 Link Image
ChEBI ID 5383 Link Image
PharmGKB ID PA449761 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02245274 Link Image
RxList Link http://www.rxlist.com/cgi/generic/glimepiride.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Glimepiride Link Image
FDA Label
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference R. Weyer et al., U.S. Pat. 4,379,785 (1981)
Average Molecular Weight 490.6160
Monoisotopic Molecular Weight 490.2250
State Solid
Melting Point 207 oC
Experimental Water Solubility Insoluble Source: PhysProp
Predicted Water Solubility 3.84e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 3.5 Source: PhysProp
Predicted LogP 2.82 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -4.11 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES CCC1=C(C)CN(C(=O)NCCC2=CC=C(C=C2)S(=O)(=O)NC(=O)N[C@H]2CC[C@H](C)CC2)C1=O
Canonical SMILES CCC1=C(C)CN(C(=O)NCCC2=CC=C(C=C2)S(=O)(=O)NC(=O)NC2CCC(C)CC2)C1=O
Drug Category
  • Anti-Arrhythmia Agents
  • Antiarrhythmic Agents
  • Hypoglycemic Agents
  • Immunosuppressive Agents
  • Sulfonylureas
ATC Codes
AHFS Codes
  • 68:20.20
Indication For concomitant use with insulin for the treatment of noninsulin-dependent (type 2) diabetes mellitus.
Pharmacology 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.
Toxicity Severe hypoglycemic reactions with coma, seizure, or other neurological impairment.
Protein Binding Over 99.5% bound to plasma protein.
Biotransformation 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.
Half Life Approximately 5 hours following single dose.
Dosage Forms
Form Route
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Cyclosporine The sulfonylurea increases the effect of cyclosporine
Gemfibrozil Gemfibrozil increases the effect and toxicity of rosiglitazone/pioglitazone
Glucosamine Possible hyperglycemia
Ketoconazole Ketoconazole increases the effect of rosiglitazone
Pregabalin Increased risk of edema
Repaglinide Similar mode of action - questionable association
Rifampin Rifampin reduces levels and efficacy of rosiglitazone, rifampin decreases the effect of sulfonylurea
Food Interactions
  • Avoid alcohol.
  • Even though food reduces product absorption, the manufacturer recommends taking the product with the first meal of the day.
Pathways Not Available
General References
  1. Wikipedia Link Image
  2. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 2C9 (CYP2C9)
Targets
  1. ATP-sensitive inward rectifier potassium channel 1
  2. ATP-sensitive inward rectifier potassium channel 11
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 2C9 (CYP2C9)
Enzyme 1 Gene Name CYP2C9
Enzyme 1 SwissProt ID P11712 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P11712|CP2C9_HUMAN Cytochrome P450 2C9 (EC 1.14.13.80) 
MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKV
YGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKW
KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS
IIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFM
KSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTE
TTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYID
LLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFK
KSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVP
PFYQLCFIPV
Drug Target 1 [top]
Target 1 ID 709
Target 1 Name ATP-sensitive inward rectifier potassium channel 1
Target 1 Synonyms
  1. ATP-regulated potassium channel ROM-K
  2. Kir1.1
  3. Potassium channel, inwardly rectifying subfamily J member 1
Target 1 Gene Name KCNJ1
Target 1 Protein Sequence >ATP-sensitive inward rectifier potassium channel 1 
MNASSRNVFDTLIRVLTESMFKHLRKWVVTRFFGHSRQRARLVSKDGRCNIEFGNVEAQS
RFIFFVDIWTTVLDLKWRYKMTIFITAFLGSWFFFGLLWYAVAYIHKDLPEFHPSANHTP
CVENINGLTSAFLFSLETQVTIGYGFRCVTEQCATAIFLLIFQSILGVIINSFMCGAILA
KISRPKKRAKTITFSKNAVISKRGGKLCLLIRVANLRKSLLIGSHIYGKLLKTTVTPEGE
TIILDQININFVVDAGNENLFFISPLTIYHVIDHNSPFFHMAAETLLQQDFELVVFLDGT
VESTSATCQVRTSYVPEEVLWGYRFAPIVSKTKEGKYRVDFHNFSKTVEVETPHCAMCLY
NEKDVRARMKRGYDNPNFILSEVNETDDTKM
Target 1 Number of Residues 397
Target 1 Molecular Weight 44795
Target 1 Theoretical pI 9.04
Target 1 GO Classification
Function
transporter activity
ion transporter activity
ion channel activity
voltage-gated ion channel activity
voltage-gated potassium channel activity
inward rectifier potassium channel activity
Process
physiological process
cellular physiological process
transport
ion transport
cation transport
monovalent inorganic cation transport
potassium ion transport
Component
cell
membrane
Target 1 General Function Involved in inward rectifier potassium channel activity
Target 1 Specific Function 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
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 78-102
  • 156-177
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 529313 Link Image
Target 1 UniProtKB/Swiss-Prot ID P48048 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name IRK1_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >1176 bp 
ATGAATGCTTCCAGTCGGAATGTGTTTGACACGTTGATCAGGGTGTTGACAGAAAGTATG
TTCAAACATCTTCGGAAATGGGTCGTCACTCGCTTTTTTGGGCATTCTCGGCAAAGAGCA
AGGCTAGTCTCCAAAGATGGAAGGTGCAACATAGAATTTGGCAATGTGGAGGCACAGTCA
AGGTTTATATTCTTTGTGGACATCTGGACAACGGTACTTGACCTCAAGTGGAGATACAAA
ATGACCATTTTCATCACAGCCTTCTTGGGGAGTTGGTTTTTCTTTGGTCTCCTGTGGTAT
GCAGTAGCGTACATTCACAAAGACCTCCCGGAATTCCATCCTTCTGCCAATCACACTCCC
TGTGTGGAGAATATTAATGGCTTGACCTCAGCTTTTCTGTTTTCTCTGGAGACTCAAGTG
ACCATTGGATATGGATTCAGGTGTGTGACAGAACAGTGTGCCACTGCCATTTTTCTGCTT
ATCTTTCAGTCTATACTTGGAGTTATAATCAATTCTTTCATGTGTGGGGCCATCTTAGCC
AAGATCTCCAGGCCCAAAAAACGTGCCAAGACCATTACGTTCAGCAAGAACGCAGTGATC
AGCAAACGGGGAGGGAAGCTTTGCCTCCTAATCCGAGTGGCTAATCTCAGGAAGAGCCTT
CTTATTGGCAGTCACATTTATGGAAAGCTTCTGAAGACCACAGTCACTCCTGAAGGAGAG
ACCATTATTTTGGACCAGATCAATATCAACTTTGTAGTTGACGCTGGGAATGAAAATTTA
TTCTTCATCTCCCCATTGACAATTTACCATGTCATTGATCACAACAGCCCTTTCTTCCAC
ATGGCAGCGGAGACCCTTCTCCAGCAGGACTTTGAATTAGTGGTGTTTTTAGATGGCACA
GTGGAGTCCACCAGTGCTACCTGCCAAGTCCGGACATCCTATGTCCCAGAGGAGGTGCTT
TGGGGCTACCGTTTTGCTCCCATAGTATCCAAGACAAAGGAAGGGAAATACCGAGTGGAT
TTCCATAACTTTAGCAAGACAGTGGAAGTGGAGACCCCTCACTGTGCCATGTGCCTTTAT
AATGAGAAAGATGTTAGAGCCAGGATGAAGAGAGGCTATGACAACCCCAACTTCATCTTG
TCAGAAGTCAATGAAACAGATGACACCAAAATGTAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID KCNJ1 Link Image
Target 1 GenAtlas ID KCNJ1 Link Image
Target 1 HGNC ID HGNC:6255 Link Image
Target 1 Chromosome Location 11
Target 1 Locus 11q24
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Krishnan SN, Desai T, Ward DC, Haddad GG: Isolation and chromosomal localization of a human ATP-regulated potassium channel. Hum Genet. 1995 Aug;96(2):155-60. [PubMed Link Image]
  2. Shuck ME, Bock JH, Benjamin CW, Tsai TD, Lee KS, Slightom JL, Bienkowski MJ: Cloning and characterization of multiple forms of the human kidney ROM-K potassium channel. J Biol Chem. 1994 Sep 30;269(39):24261-70. [PubMed Link Image]
  3. Yano H, Philipson LH, Kugler JL, Tokuyama Y, Davis EM, Le Beau MM, Nelson DJ, Bell GI, Takeda J: Alternative splicing of human inwardly rectifying K+ channel ROMK1 mRNA. Mol Pharmacol. 1994 May;45(5):854-60. [PubMed Link Image]
  4. Mutations in the gene encoding the inwardly-rectifying renal potassium channel, ROMK, cause the antenatal variant of Bartter syndrome: evidence for genetic heterogeneity. International Collaborative Study Group for Bartter-like Syndromes. Hum Mol Genet. 1997 Jan;6(1):17-26. [PubMed Link Image]
Target 1 Drug References
  1. 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 Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 781
Target 2 Name ATP-sensitive inward rectifier potassium channel 11
Target 2 Synonyms
  1. IKATP
  2. Inward rectifier K(+) channel Kir6.2
  3. Potassium channel, inwardly rectifying subfamily J member 11
Target 2 Gene Name KCNJ11
Target 2 Protein Sequence >ATP-sensitive inward rectifier potassium channel 11 
MLSRKGIIPEEYVLTRLAEDPAEPRYRARQRRARFVSKKGNCNVAHKNIREQGRFLQDVF
TTLVDLKWPHTLLIFTMSFLCSWLLFAMAWWLIAFAHGDLAPSEGTAEPCVTSIHSFSSA
FLFSIEVQVTIGFGGRMVTEECPLAILILIVQNIVGLMINAIMLGCIFMKTAQAHRRAET
LIFSKHAVIALRHGRLCFMLRVGDLRKSMIISATIHMQVVRKTTSPEGEVVPLHQVDIPM
ENGVGGNSIFLVAPLIIYHVIDANSPLYDLAPSDLHHHQDLEIIVILEGVVETTGITTQA
RTSYLADEILWGQRFVPIVAEEDGRYSVDYSKFGNTIKVPTPLCTARQLDEDHSLLEALT
LASARGPLRKRSVPMAKAKPKFSISPDSLS
Target 2 Number of Residues 396
Target 2 Molecular Weight 43541
Target 2 Theoretical pI 8.10
Target 2 GO Classification
Function
ATP-activated inward rectifier potassium channel activity
transporter activity
ion transporter activity
ion channel activity
voltage-gated ion channel activity
voltage-gated potassium channel activity
inward rectifier potassium channel activity
Process
physiological process
cellular physiological process
transport
ion transport
cation transport
monovalent inorganic cation transport
potassium ion transport
Component
cell
membrane
Target 2 General Function Involved in inward rectifier potassium channel activity
Target 2 Specific Function 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
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 69-93
  • 145-166
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 1088445 Link Image
Target 2 UniProtKB/Swiss-Prot ID Q14654 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name IRK11_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 2 Gene Sequence >1173 bp 
ATGCTGTCCCGCAAGGGCATCATCCCCGAGGAATACGTGCTGACACGCCTGGCAGAGGAC
CCTGCCGAGCCCAGGTACCGTGCCCGCCAGCGGAGGGCCCGCTTTGTGTCCAAGAAAGGC
AACTGCAACGTGGCCCACAAGAACATCCGGGAGCAGGGCCGCTTCCTGCAGGACGTGTTC
ACCACGCTGGTGGACCTCAAGTGGCCACACACATTGCTCATCTTCACCATGTCCTTCCTG
TGCAGCTGGCTGCTCTTCGCCATGGCCTGGTGGCTCATCGCCTTCGCCCACGGTGACCTG
GCCCCCAGCGAGGGCACTGCTGAGCCCTGTGTCACCAGCATCCACTCCTTCTCGTCTGCC
TTCCTTTTCTCCATTGAGGTCCAAGTGACTATTGGCTTTGGGGGGCGCATGGTGACTGAG
GAGTGCCCACTGGCCATCCTGAGCCTCATCGTGCAGAACATCGTGGGGCTCATGATCAAC
GCCATCATGCTTGGCTGCATCTTCATGAAGACTGCCCAAGCCCACCGCAGGGCTGAGACC
CTCATCTTCAGCAAGCATGCGGTGATCGCTCTGCGCCACGGCCGCCTCTGCTTCATGCTA
CGTGTGGGTGACCTCCGCAAGAGCATGATCATCAGCGCCACCATCCACATGCAGGTGGTA
CGCAAGACCACCAGCCCCGAGGGCGAGGTGGTGCCCCTCCACCAGGTGGACATCCCCATG
GAGAACGGCGTGGGTGGCAACAGCATCTTCCTGGTGGCCCCGCTGATCATCTACCATGTC
ATTGATGCCAACAGCCCACTCTACGACCTGGCACCCAGCGACCTGCACCACCACCAGGAC
CTCGAGATCATCGTCATCCTGGAAGGCGTGGTGGAAACCACGGGCATCACCACCCAGGCC
CGCACCTCCTACCTGGCCGATGAGATCCTGTGGGGCCAGCGCTTTGTGCCCATTGTAGCT
GAGGAGGACGGACGTTACTCTGTGGACTACTCCAAGTTTGGCAACACCATCAAAGTGCCC
ACACCACTCTGCACGGCCCGCCAGCTTGATGAGGACCACAGCCTACTGGAAGCTCTGACC
CTCGCCTCAGCCCGCGGGCCCCTGCGCAAGCGCAGCGTGCCCATGGCCAAGGCCAAGCCC
AAGTTCAGCATCTCTCCAGATTCCCTGTCCTGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID KCNJ11 Link Image
Target 2 GenAtlas ID KCNJ11 Link Image
Target 2 HGNC ID HGNC:6257 Link Image
Target 2 Chromosome Location 11
Target 2 Locus 11p15.1
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Aguilar-Bryan L, Bryan J: Molecular biology of adenosine triphosphate-sensitive potassium channels. Endocr Rev. 1999 Apr;20(2):101-35. [PubMed Link Image]
  2. Meissner T, Beinbrech B, Mayatepek E: Congenital hyperinsulinism: molecular basis of a heterogeneous disease. Hum Mutat. 1999;13(5):351-61. [PubMed Link Image]
  3. Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, Cooper R, Lipshutz R, Chakravarti A: Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nat Genet. 1999 Jul;22(3):239-47. [PubMed Link Image]
  4. Inagaki N, Gonoi T, Clement JP 4th, Namba N, Inazawa J, Gonzalez G, Aguilar-Bryan L, Seino S, Bryan J: Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science. 1995 Nov 17;270(5239):1166-70. [PubMed Link Image]
  5. Thomas PM, Cote GJ, Hallman DM, Mathew PM: Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy. Am J Hum Genet. 1995 Feb;56(2):416-21. [PubMed Link Image]
  6. Sakura H, Wat N, Horton V, Millns H, Turner RC, Ashcroft FM: Sequence variations in the human Kir6.2 gene, a subunit of the beta-cell ATP-sensitive K-channel: no association with NIDDM in while Caucasian subjects or evidence of abnormal function when expressed in vitro. Diabetologia. 1996 Oct;39(10):1233-6. [PubMed Link Image]
  7. Inoue H, Ferrer J, Warren-Perry M, Zhang Y, Millns H, Turner RC, Elbein SC, Hampe CL, Suarez BK, Inagaki N, Seino S, Permutt MA: Sequence variants in the pancreatic islet beta-cell inwardly rectifying K+ channel Kir6.2 (Bir) gene: identification and lack of role in Caucasian patients with NIDDM. Diabetes. 1997 Mar;46(3):502-7. [PubMed Link Image]
Target 2 Drug 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 Link Image]
  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 Link Image]

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.