Document Detail


Vernakalant, a mixed sodium and potassium ion channel antagonist that blocks K(v)1.5 channels, for the potential treatment of atrial fibrillation.
MedLine Citation:
PMID:  20730700     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
George E Billman
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Current opinion in investigational drugs (London, England : 2000)     Volume:  11     ISSN:  2040-3429     ISO Abbreviation:  Curr Opin Investig Drugs     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-23     Completed Date:  2011-02-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100965718     Medline TA:  Curr Opin Investig Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  1048-58     Citation Subset:  IM    
Affiliation:
Department of Physiology and Cell Biology, The Ohio State University, Columbus OH 43210-1218, USA. billman.1@osu.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Anisoles / adverse effects,  metabolism,  pharmacokinetics,  therapeutic use*
Atrial Fibrillation / drug therapy*,  metabolism
Clinical Trials as Topic
Dogs
Drug Evaluation, Preclinical
Humans
Kv1.5 Potassium Channel / antagonists & inhibitors*
Macaca fascicularis
Male
Potassium Channel Blockers / adverse effects,  metabolism,  pharmacokinetics,  therapeutic use*
Pyrrolidines / adverse effects,  metabolism,  pharmacokinetics,  therapeutic use*
Rabbits
Sodium Channel Blockers / adverse effects,  metabolism,  pharmacokinetics,  therapeutic use*
Chemical
Reg. No./Substance:
0/Anisoles; 0/Kv1.5 Potassium Channel; 0/Potassium Channel Blockers; 0/Pyrrolidines; 0/Sodium Channel Blockers; 0/vernakalant

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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