Inhibitory effects of the antihistamines epinastine, terfenadine, and ebastine on potassium currents in rat ventricular myocytes

We examined and compared the inhibitory effects of three non-sedating antih istamines, terfenadine, ebastine, and epinastine, on delayed rectifier pota ssium current (I-K) and transient outward potassium current (I-to) of rat i solated ventricular myocytes, using a patch clamp technique. Terfenadine, ebastine and epinastine were found to inhibit I-K With IC50 va lues of 5.96, 15.3 and 145 mu M, respectively. I-to was suppressed by epina stine with an IC50 value of 69.5 mu M. The order of arrhythmogenicity, asse ssed by the inhibition of I-K, was ranked as terfenadine > ebastine > epina stine, consistent with that of the potencies of each drug for QT prolongati on reported in rats.