Vernakalant, a mixed sodium and potassium ion channel antagonist that blocks K(v)1.5 channels, for the potential treatment of atrial fibrillation.
Despite being the most common arrhythmia currently treated by cardiologists, safe and effective treatments for atrial fibrillation (AF) remain elusive. To address this issue, Astellas Pharma Inc, Merck & Co Inc and Cardiome Pharma Corp are developing vernakalant (RSD-1235), a drug which dose-dependently inhibits sodium channels and several potassium repolarizing currents. Of particular note, vernakalant inhibits I(Kur) (K(v)1.5), a current that is more predominant in atrial than in ventricular tissue. Consistent with this observation, vernakalant produced increases in atrial refractory period with minimal actions on QTc interval or ventricular refractory period in both humans and animals. Intravenous vernakalant terminated recent-onset AF in several animal models, and also in patients with short-duration AF or AF following cardiac surgery enrolled in phase II and III clinical trials. Vernakalant was well tolerated and adverse reactions were transient and mild. Thus, vernakalant holds considerable promise for the treatment of recent-onset AF; however, given its relatively short half-life, continuous dosing may be required in order to maintain sinus rhythm following conversion from AF. The efficacy and safety of vernakalant for the long-term management of AF remains to be determined. Phase III clinical trials with intravenous vernakalant are ongoing, and phase II clinical trials are also being conducted with an oral formulation intended for chronic use.
Billman
George E
GE
Department of Physiology and Cell Biology, The Ohio State University, Columbus OH 43210-1218, USA. billman.1@osu.edu
D000818:Animals; D000840:Anisoles / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D006801:Humans; D051666:Kv1.5 Potassium Channel / Q000037:antagonists & inhibitors*; D008252:Macaca fascicularis; D008297:Male; D026902:Potassium Channel Blockers / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011817:Rabbits; D026941:Sodium Channel Blockers / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000840:Anisoles; D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers; D011759:Pyrrolidines; D026941:Sodium Channel Blockers; C524581:vernakalant