| 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 |
|
| Name |
Glimepiride |
| Drug Type |
|
| Description |
Glimepiride is the first III generation sulphonyl urea it is a very potent sulphonyl urea with long duration of action. |
| Synonyms |
- Glimepirid
- Glimepirida
- Glimepiridum
- Glimepride
|
| Brand Names |
- Amarel
- Amaryl
- Endial
- Novo-glimepiride
- PMS-glimepiride
- Ratio-glimepiride
- Sandoz glimepiride
|
| Brand Mixtures |
- 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 |
 |
| 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  |
| KEGG Compound |
C07669  |
| PubChem Compound |
3476  |
| PubChem Substance |
193913  |
| ChEBI ID |
5383  |
| PharmGKB ID |
PA449761  |
| HET ID |
Not Available |
| GenBank ID |
Not Available |
| Drug ID Number [DIN] |
02245274  |
| RxList Link |
http://www.rxlist.com/cgi/generic/glimepiride.htm  |
| PDRhealth Link |
Not Available |
| Wikipedia Link |
http://en.wikipedia.org/wiki/Glimepiride  |
| 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 | Download  |
| SDF File |
Show | Download  |
| PDB File |
Show | Download  |
| 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 |
|
| 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 |
|
| Patient Information |
Show  |
| Contraindications |
Show  |
| Interactions |
Show  |
| 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 |
- Wikipedia

- RxList

|
| Organisms Affected |
|
| Phase 1 Metabolizing Enzymes |
- Cytochrome P450 2C9 (CYP2C9)
|
| Targets |
- ATP-sensitive inward rectifier potassium channel 1
- ATP-sensitive inward rectifier potassium channel 11
|
|
Drug Target 1
[top]
|
| Target 1 ID |
709 |
| Target 1 Name |
ATP-sensitive inward rectifier potassium channel 1 |
| Target 1 Synonyms |
- ATP-regulated potassium channel ROM-K
- Kir1.1
- 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 |
|
| Target 1 Transmembrane Regions |
|
| Target 1 Essentiality |
Non-Essential |
| Target 1 GenBank ID Protein |
529313  |
| Target 1 UniProtKB/Swiss-Prot ID |
P48048  |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
IRK1_HUMAN  |
| 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  |
| Target 1 GenAtlas ID |
KCNJ1  |
| Target 1 HGNC ID |
HGNC:6255  |
| Target 1 Chromosome Location |
11 |
| Target 1 Locus |
11q24 |
| Target 1 SNPs |
SNPJam Report  |
| Target 1 General References |
- 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
]
- 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
]
- 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
]
- 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
]
|
| Target 1 Drug References |
- 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
]
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed
]
|
|
Drug Target 2
[top]
|
| Target 2 ID |
781 |
| Target 2 Name |
ATP-sensitive inward rectifier potassium channel 11 |
| Target 2 Synonyms |
- IKATP
- Inward rectifier K(+) channel Kir6.2
- 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 |
|
| Target 2 Transmembrane Regions |
|
| Target 2 Essentiality |
Non-Essential |
| Target 2 GenBank ID Protein |
1088445  |
| Target 2 UniProtKB/Swiss-Prot ID |
Q14654  |
| Target 2 UniProtKB/Swiss-Prot Entry Name |
IRK11_HUMAN  |
| 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  |
| Target 2 GenAtlas ID |
KCNJ11  |
| Target 2 HGNC ID |
HGNC:6257  |
| Target 2 Chromosome Location |
11 |
| Target 2 Locus |
11p15.1 |
| Target 2 SNPs |
SNPJam Report  |
| Target 2 General References |
- Aguilar-Bryan L, Bryan J: Molecular biology of adenosine triphosphate-sensitive potassium channels. Endocr Rev. 1999 Apr;20(2):101-35. [PubMed
]
- Meissner T, Beinbrech B, Mayatepek E: Congenital hyperinsulinism: molecular basis of a heterogeneous disease. Hum Mutat. 1999;13(5):351-61. [PubMed
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
|
| Target 2 Drug References |
- 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
]
- 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
]
|