Vernakalant Hydrochloride is a mixed voltage- and frequency-dependent Na+ and atria-preferred K+ channel blocker.
Block of Kv1.5 by Vernakalant Hydrochloride is mediated after channel activation because Vernakalant causes a relatively rapid onset of a block of channel current upon depolarization but little evidence of resting or “tonic” block of the channel. The most important effect is the reduction in potency for Vernakalant centered at I502A, which had an IC50 of 329±19 μM (n=4-10), compared with a control IC50 of 13.4±0.9 μM (n=5-23), which is a 25-fold decrease in potency. V505A, I508A, T480A, and C500A showed lesser reductions in potency on Kv1.5, of between 3- and 4-fold. IC50 for block by Vernakalant of wild-type and mutant Kv1.5 channels Fractional block is 13.35±0.93 μM, 0.61±0.03 μM, and 1.63±0.09 μM for Kv1.5 channels, Kv1.5 channelI508F, Kv1.5 channelT479A, respectively .