Adekalant tartrate

Adekalant, also known as H 345/52. is a new antiarrhythmic compound with low proarrhythmic activity. Adekalant concentration-dependently blocked HERG-carried currents with an IC50 of 230 nM. Adekalant preferentially bound to the open channel with unusually rapid kinetics and was trapped by channel closure. Voltage-independent behavior of Adekalant was observed during both square-pulse and action potential clamp protocols. It is proposed that block of I(Kr) is the principal mechanism by which Adekalant delays repolarization in human myocardium. Adekalant blocks I(Kr) with high potency and I(Ca) with somewhat lower potency and was found to delay ventricular repolarization without substantially increasing temporal or spatial dispersion and without inducing early after-depolarizations or TdP.