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