Vernakalant

Vernakalant blocks atrial voltage-gated sodium channels in a dose and frequency-dependent manner and inhibits late sodium current (INa)which confers its effect on intra-atrial conduction. This current blockade enhance and onset of drug action accelerates in higher heart rate as the affinity of vernakalant for INa also increases. Its binding offset is quick once the heart rate slows. It also blocks Kv 1.5 channel and its early activating potassium channels (IKur) and inhibits acetylcholine-activated potassium channels (IKAch), which are specific to the atrium and cause prolongation of atrial refractoriness. Vernakalant also blocks Kv4.3 channel and its cardiac transient outward potassium current (Ito), which is involved more with atrial than ventricular refractoriness. Vernakalant minimally blocks hERG channels and its rapidly activating/delayed rectifying potassium current (IKr) which accounts for mild QT prolongation. QRS widening due to INa blockade also contributes to QT prolongation.