Descarboethoxyloratadine blocks human cardiac Kv1.5 channels in a concentration-, voltage-, and time-dependent manner, which may have implications for cardiac electrophysiology.
DCL may affect atrial repolarization; hypothesis-generating for clinical arrhythmia risk in humans.
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 microM) inhibited hKv1.5 current in a concentration-dependent manner with an apparent affinity constant of 12.5+/-1.2 microM. The blockade increased steeply over the voltage range of channel opening, which indicated that DCL binds preferentially to the open state of the channel. At more depolarized potentials a weaker voltage-dependence was observed consistent with a binding reaction sensing approximately 20% of the transmembrane electrical field. DCL, 20 microM, 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.
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Caballero et al. (1997) studied this question.
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