CPU-228

CPU-228 is a complex class III antiarrhythmic agent. CPU-228 concentration-dependently blocks the activities of the rapid component 50 of the delayed rectifier potassium channel (I_Kr) and the L-type calcium channel (I_Ca,L), with an IC₅₀ value of 0.909 μM for I_Ca,L current. CPU-228 produces negative inotropic effects and induces mild, non-frequency-dependent prolongation of the effective refractory period (ERP) in isolated left atria. CPU-228 reduces the incidence of torsades de pointes (TDP) in anesthetized rabbits and inhibits ischemia/reperfusion-induced arrhythmias in rats. CPU-228 can be used in studies related to torsades de pointes^[1]. In Vitro:CPU-228 (0.01-1 μM) concentration-dependently blocks I_Kr in isolated guinea pig ventricular myocytes without altering the activities of I_Ks or I_K1^[1].
CPU-228 (0.33-10 μM) concentration-dependently blocks I_Ca,L in isolated guinea pig ventricular myocytes, with an IC₅₀ of 0.909 μM. It also alters the kinetic properties of I_Ca,L by shifting the steady-state inactivation curve to more negative potentials, without affecting its activation characteristics^[1].
CPU-228 (3.3 μM; 5 min) significantly inhibits systolic cytoplasmic calcium transients in isolated rat ventricular myocytes without altering diastolic calcium levels or the decay kinetics of calcium transients^[1].
CPU-228 (10 nM-100 μM; 15 min) concentration-dependently prolongs the ERP of isolated left atria in guinea pigs without reverse frequency dependence; within the pacing frequency range of 0.5-2.0 Hz, it induces a 23%-24% prolongation at the concentration of 100 μM^[1].
CPU-228 (10 nM-100 μM) exerts a concentration-dependent negative inotropic effect on isolated left atria of guinea pigs, with an IC₅₀ of 69.2 μM, and significantly reduces contractile force at 100 μM^[1].