DT-Web

DB01289 - Glisoxepide


Identification
Name Glisoxepide
Accession Number DB01289
Type small molecule
Description Glisoxepide is one of the sulphonamide-derived oral antidiabetic drugs. It inhibits the uptake of bile acids into isolated rat hepatocytes. However it inhibits taurocholate uptake only in the absence of sodium ions. Glisoxepide uptake could be further inhibited by blockers of the hepatocellular monocarboxylate transporter, by the loop diuretic bumetanide, by 4,4'-diisothiocyano-2,2'-stilbenedisulfonate (DIDS) and by sulphate. These results are consistent with the transport of glisoxepide via the transport system for the unconjugated bile acid cholate. (PMID:1618280, 9017793)
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 449.524
Groups approved
Monoisotopic Weight 449.173289689
Pharmacology
Indication For the treatment of diabetes mellitus type 2.
Mechanism of action Glisoxepide is a hypoglycemic sulphonylurea agent. The sulphonylureas are a family of drugs based on a common sulphonylurea core. These drugs act via augmentation of secretion of insulin from pancreatic beta-cells. Sulphonylureas may also cause a reduction in serum glucagon and potentiate the action of insulin at the extrapancreatic tissues. Glisoxepide functions as a non-selective K(ATP) channel blocker. It is thought to stimulate insulin secretion by closing the ATP-sensitive K(+) (K(ATP)) channels (Kir6.2/SUR1 complex, KATP channels) in pancreatic beta-cells. This inhibits a tonic, hyperpolarizing efflux of potassium, thus causing the electric potential over the membrane to become more positive. This depolarization opens voltage-gated Ca2+ channels. The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane, and therefore increased secretion of (pro)insulin.
Absorption Not Available
Protein binding Not Available
Biotransformation Not Available
Route of elimination Not Available
Toxicity Not Available
Affected organisms Not Available
Interactions
Drug Interactions
Drug Mechanism of interaction
Acebutolol The beta-blocker, acebutolol, may decrease symptoms of hypoglycemia.
Acetylsalicylic acid Acetylsalicylic acid increases the effect of the sulfonylurea, glisoxepide.
Atenolol The beta-blocker, atenolol, may decrease symptoms of hypoglycemia.
Bisoprolol The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.
Carvedilol The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Chloramphenicol Chloramphenicol may increase the effect of sulfonylurea, glisoxepide.
Clofibrate Clofibrate may increase the effect of sulfonylurea, glisoxepide.
Esmolol The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.
Labetalol The beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
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.
Phenylbutazone Phenylbutazone increases the effect of the hypoglycemic agent
Pindolol The beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
Propranolol The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.
Rifampin Rifampin may decrease the effect of sulfonylurea, glisoxepide.
Timolol The beta-blocker, timolol, may decrease symptoms of hypoglycemia.
Food Interactions Not Available

Targets


ATP-sensitive inward rectifier potassium channel 8
Name ATP-sensitive inward rectifier potassium channel 8
Gene Name KCNJ8
Pharmacological action yes
Actions inhibitor
References
  • Szewczyk A, Wojcik G, Lobanov NA, Nalecz MJ: The mitochondrial sulfonylurea receptor: identification and characterization. Biochem Biophys Res Commun. 1997 Jan 23;230(3):611-5. - Pubmed
  • Sato T, Costa AD, Saito T, Ogura T, Ishida H, Garlid KD, Nakaya H: Bepridil, an antiarrhythmic drug, opens mitochondrial KATP channels, blocks sarcolemmal KATP channels, and confers cardioprotection. J Pharmacol Exp Ther. 2006 Jan;316(1):182-8. Epub 2005 Sep 20. - Pubmed
DTHybrid score 0.6715

Predictions


Id Partner name Gene Name Score
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.116
230 ATP-binding cassette transporter sub-family C member 8 ABCC8 0.0963
1561 Troponin C, slow skeletal and cardiac muscles TNNC1 0.0534
748 5'-AMP-activated protein kinase catalytic subunit alpha-1 PRKAA1 0.0481
485 cGMP-inhibited 3',5'-cyclic phosphodiesterase A PDE3A 0.0461
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0329
6144 Solute carrier family 22 member 2 SLC22A2 0.0265
6145 Solute carrier family 22 member 1 SLC22A1 0.0254
4757 Cytochrome P450 2C9 CYP2C9 0.0246
4119 Cytochrome P450 2D6 CYP2D6 0.0191
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