Ibutilide (U70226E free base) is a potent antiarrhythmic compound that extends the action potential duration. It effectively blocks the rapidly activating delayed rectifier potassium current (I Kr ) in AT-1 cells [1].

Ibutilide is a potent IKr blocker with EC 50 value of 20 nM at +20 mV in atrial tumor myocytes (AT-1) cells [1]. Ibutilide blocks I Kr in cells expressing HERG+MDR1*1 to the same extent as cells expressing HERG alone (IC 50 : 22.5±0.9 vs 27.4±2.5 nM). However, cells expressing MDR1*7 show a marked resistance to Ibutilide (IC 50 : 105.3±1.42 nM vs 27.4±2.5 nM) [2].

Ibutilide effectively prolongs cardiac repolarization both in vitro and in vivo, with its administration in cumulative doses (0.01, 0.02, and 0.05 mg/kg i.v., each delivered over 10 minutes) inducing both polymorphic and monomorphic non-sustained ventricular tachycardia. In a study involving fifteen adult mongrel dogs of either sex, it was shown that at a dosage of 0.01 mg/kg, Ibutilide significantly extends the action potential duration at 90% (APD90) in subjects with congestive heart failure (CHF) compared to controls. Furthermore, this dosage resulted in an increased dispersion of left-right ventricular APD90 in CHF subjects, an effect not observed in the control group.