Effect of descarboethoxyloratadine, the major metabolite of loratadine, on the human cardiac potassium channel Kv1.5

The effects of descarboethoxyloratadine (DCL), the major metabolite of loratadine, were studied on a human cardiac K+ channel (hKv1.5) cloned from human ventricle and stably expressed in a mouse cell line by means of the patch-clamp technique. DCL (1-100 mu M) inhibited hKv1.5 current in a concentration-dependent manner with an apparent affinity constant of 12.5+/-1.2 mu M. The blockade increased steeply over the voltage range of channel opening, which indicated that DCL binds preferentially to the open state of the channel. Al more depolarized potentials a weaker voltage dependence was observed consistent with a binding reaction sensing approximate to 20% of the transmembrane electrical field. DCL, 20 mu M, increased the time constant of deactivation of tail currents, thus inducing a 'crossover' phenomenon. The present results demonstrated that DCL blocked hKv1.5 channels in a concentration-, voltage-, and time-dependent manner.