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Pathway Description
Tolazamide Action Pathway
Homo sapiens
Drug Action Pathway
Tolazamide is an hypoglycemic agent from the sulfonylurea class used in the treatment of non insulin dependent diabetes mellitus type II. Tolazamide lowers blood glucose by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. This drug binds to ATP-sensitive potassium-channel receptors on the pancreatic cell surface (known as the sulfonylurea receptor 1 (SUR1) subunit (Kir6.2)), reducing potassium conductance and causing depolarization of the membrane. This depolarization stimulates the calcium ion influx through voltage-sensitive calcium channels thus raising intracellular concentrations of calcium ions. The higher concentration of intracellular calcium ions induces the secretion (exocytosis) of insulin into the blood. Tolazamide is administered as an oral tablet.
References
Tolazamide Pathway References
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Tal A: Oral hypoglycemic agents in the treatment of type II diabetes. Am Fam Physician. 1993 Nov 1;48(6):1089-95.
Pubmed: 8237731
Granberry MC, Fonseca VA: Cardiovascular risk factors associated with insulin resistance: effects of oral antidiabetic agents. Am J Cardiovasc Drugs. 2005;5(3):201-9. doi: 10.2165/00129784-200505030-00006.
Pubmed: 15901207
Szabo C, Salzman AL: Inhibition of ATP-activated potassium channels exerts pressor effects and improves survival in a rat model of severe hemorrhagic shock. Shock. 1996 Jun;5(6):391-4. doi: 10.1097/00024382-199606000-00001.
Pubmed: 8799949
Asano K, Cortes P, Garvin JL, Riser BL, Rodriguez-Barbero A, Szamosfalvi B, Yee J: Characterization of the rat mesangial cell type 2 sulfonylurea receptor. Kidney Int. 1999 Jun;55(6):2289-98. doi: 10.1046/j.1523-1755.1999.00485.x.
Pubmed: 10354277
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