limited success of highly specific drugs that target single ion channels and
the efficacy of multi-ion channel blockers such as amiodarone have shifted the
emphasis in antiarrhythmic drug development to the latter class of drugs.
Vernakalant is a multi-ion channel blocker that was developed for the treatment
of atrial fibrillation.
prolongs the atrial effective refractory period and slows conduction over the
AV node. Ventricular effective refrac-tory period is unchanged. In the maximal
clinical dose of 1800 mg/day, vernakalant does not change the QT interval on
the ECG. Vernakalant blocks IKur, IACh, and Ito.
These currents play key roles in atrial repolarization and their block accounts
for the prolongation of the atrial effective refractory period. The drug is a
less potent blocker of IKr and, as a result, produces less APD
pro-longation in the ventricle; that is, the APD-prolonging effect is
relatively atrium specific. Vernakalant also produces use-dependent block of
the sodium channel. Recovery from block is fast, such that significant blockade
is observed only at fast rates or at low membrane potentials. In the
therapeutic concentration range, vernakalant has no effect on heart rate.
effects of vernakalant include dysgeusia (disturbance of taste), sneezing,
paresthesia, cough, and hypotension.
data for vernakalant are limited. After IV admin-istration, the drug is metabolized
in the liver by CYP2D6 with a half-life of 2 hours. However, on an oral regimen
of 900 mg twice daily, a sustained blood concentration was observed over a
12-hour interval. Clinical trials with the oral drug have used a twice-daily
vernakalant is effective in converting recent-onset atrial fibrillation to
normal sinus rhythm in 50% of patients. Final approval for this purpose is
pending. The drug is undergoing clinical trials for maintenance of normal sinus
rhythm in patients with paroxysmal or persistent atrial fibrillation.