(4-甲氧基苄基)(1-萘基甲基)胺盐酸盐

ML133 HCl是一种选择性钾离子通道抑制剂，作用于K_ir2.1， IC50为1.8 μM (pH 7.4)和290 nM (pH 8.5)，对K_ir1.1没有作用效果，对K_ir4.1和K_ir7.1具有微弱的作用活性。 The ratio of total concentration of extracellular ML133 versus intracellular ML133 is 1:0.13 at pH 6.5, 1:9.09 at pH 8.5. ML133 is clean against 3A4 and 2C9 (IC50 >30 μM), displays moderate inhibition of 1A2 (IC50 = 3.3 μM) but proves to be a potent inhibitor of 2D6 (IC50 = 0.13 μM) in CYP450 assay. ML133 is highly protein bound (>99%) in both human and rat and also displays high intrinsic clearance in both species. ML133 (10 μM) is not displaced by K⁺ influx from the wild-type K_ir2.1 in HEK 293 cells. M1 and/or M2 transmembrane domains contain the critical molecular determinant for ML133 inhibition of K_ir2.1, especially D172 and I176.