Tifenazoxide (NN414) is a potent, orally active and SUR1/Kir6.2 selective K^ATP channels opener. Tifenazoxide has antidiabetic effect, can inhibit glucose stimulated insulin release in vitro and in vivo, and has a beneficial effect on glucose homeostasis^[1][2]. IC50 & Target: K^ATP channels^[1][2] In Vitro: Tifenazoxide (NN414) hyperpolarises βTC3 cell membranes, and inhibits insulin release from βTC6, from isolated rat islets and from human islets at least a 100-fold more potent than Diazoxide^[2].
The EC₅₀ values for Tifenazoxide and diazoxide are 0.45 and 31 µM, respectively in the patch-clamp assay. Tifenazoxide (100 µM) activates Kir6.2/SUR1 channels, but not Kir6.2/SUR2A or Kir6.2/SUR2 channels, expressed in Xenopus oocytes both in whole-cell and inside-out macropatch recordings^[2].
Tifenazoxide is a potent inhibitor of glucose stimulated insulin release from βTC6 cells (IC₅₀ = 0.15 µM)^[1]. In Vivo: Tifenazoxide (NN414; 1.5 mg/kg; oral administration; twice daily; for 3 weeks; male VDF Zucker (fa/fa) rat) treatment for 3 weeks in VDF rats reduces basal hyperglycemia, improves glucose tolerance, and reduces hyperinsulinemia during an oral glucose tolerance test (OGTT) and improves insulin secretory responsiveness ex vivo^[1].