Tolazamide is a first generation sulfonylurea that inhibits sulfonylurea receptor 1 (SUR1) linked to the inwardly rectifying potassium channel (KIR6.2; IC50 = 4.2 ?M in HEK293 cells transfected with the human receptor).1 It has no effect on glucose uptake in L6 rat skeletal muscle cells when used at a concentration of 0.6 mg/mL but enhances glucose uptake two-fold when used in combination with insulin.2 In vivo, tolazamide (128 mg/kg) reduces glomerulosclerosis and albumin excretion in a rat model of insulin-dependent diabetes induced by streptozotocin .3 Formulations containing tolazamide have been used in the treatment of type 2 diabetes.
1.Gopalakrishnan, M., Molinari, E.J., Char-Change, S., et al.Pharmacology of human sulphonylurea receptor SUR1 and inward rectifier K+ channel Kir6.2 combination expressed in HEK-293 cellsBr. J. Pharmacol.129(7)1323-1332(2000) 2.Wang, P.H., Moeller, D., Flier, J.S., et al.Coordinate regulation of glucose transporter function, number, and gene expression by insulin and sulfonylureas in L6 rat skeletal muscle cellsJ. Clin. Invest.84(1)62-67(1989) 3.Biederman, J.I., Vera, E., Rankhaniya, R., et al.Effects of sulfonylureas, α-endosulfine counterparts, on glomerulosclerosis in type 1 and type 2 models of diabetesKidney Int.67(2)554-565(2005)