View source for Vernakalant

{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 446573380
| IUPAC_name = (3''R'')-1-{(1''R'',2''R'')-2-[2-(3,4-dimethoxyphenyl)<br>ethoxy]cyclohexyl}pyrrolidin-3-ol
| image = Vernakalant.png

<!--Clinical data-->
| tradename =  
| licence_EU = Brinavess
| licence_US = <!-- FDA may use generic name -->
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B            / C / D / X -->
| pregnancy_category =  
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA = <!--             / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL         / P       / POM / CD / Class A, B, C -->
| legal_US = <!-- OTC                   / Rx-only  / Schedule I, II, III, IV, V -->
| legal_status = Rx-only
| routes_of_administration = [[Intravenous therapy|Intravenous]], oral

<!--Pharmacokinetic data-->
| bioavailability =  
| protein_bound =  
| metabolism =  
| elimination_half-life =  
| excretion =  

<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 794466-70-9
| CAS_supplemental = <br />{{CAS|748810-28-8}} ([[hydrochloride|HCl]])
| ATC_prefix = C01
| ATC_suffix = BG11
| PubChem = 9930049
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank =  
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 9G468C8B13
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID      = 8105680
| smiles            = O(c1ccc(cc1OC)CCO[C@@H]3CCCC[C@H]3N2CC[C@@H](O)C2)C
| InChI             = 1/C20H31NO4/c1-23-19-8-7-15(13-20(19)24-2)10-12-25-18-6-4-3-5-17(18)21-11-9-16(22)14-21/h7-8,13,16-18,22H,3-6,9-12,14H2,1-2H3/t16-,17-,18-/m1/s1
| InChIKey          = VBHQKCBVWWUUKN-KZNAEPCWBT
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI          = 1S/C20H31NO4/c1-23-19-8-7-15(13-20(19)24-2)10-12-25-18-6-4-3-5-17(18)21-11-9-16(22)14-21/h7-8,13,16-18,22H,3-6,9-12,14H2,1-2H3/t16-,17-,18-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey       = VBHQKCBVWWUUKN-KZNAEPCWSA-N

<!--Chemical data-->
| C=20 | H=31 | N=1 | O=4 
| molecular_weight = 349.464 g/mol
}}
__NOTOC__
{{SI}}
{{CMG}}

==Overview==
'''Vernakalant''' ([[International Nonproprietary Name|INN]]; codenamed '''RSD1235''', proposed tradenames '''Kynapid''' and '''Brinavess''') is an investigational drug under regulatory review for the acute conversion of [[atrial fibrillation]]. It was initially developed by [[Cardiome Pharma]], and the [[intravenous]] formulation has been bought for further development by [[Merck & Co.|Merck]] in April 2009.<ref name="FierceBiotech">{{cite news|url=http://www.fiercebiotech.com/press-releases/merck-and-cardiome-pharma-sign-license-agreement-vernakalant-investigational-drug-tre|title=Merck and Cardiome Pharma Sign License Agreement for Vernakalant, an Investigational Drug for Treatment of Atrial Fibrillation|date=9 April 2009|accessdate=12 October 2010|publisher=FierceBiotech}}</ref>

On December 11, 2007, the Cardiovascular and Renal Drugs Advisory Committee of the [[United States|US]] [[Food and Drug Administration]] (FDA) voted to recommend the approval of vernakalant,<ref>{{cite web |url=http://www.drugs.com/nda/kynapid_071212.html |title=FDA Advisory Committee Recommends Approval of Kynapid for Acute Atrial Fibrillation
 |accessdate=2008-03-15 |publisher=Drugs.com }}</ref> but in August 2008 the FDA judged that additional information was necessary for approval.<ref name="FierceBiotech" />
The drug was approved in Europe on September 1, 2010.<ref>{{cite press release
  | title = BRINAVESS (vernakalant) for Infusion Approved in the European Union for Rapid Conversion of Recent Onset Atrial Fibrillation
  | publisher = Merck & Co., Inc.
  | date = 2010-09-01
  | url = http://www.merck.com/newsroom/news-release-archive/research-and-development/2010_0901.html
  | accessdate = September 28, 2010  
}}</ref>

An oral formulation underwent Phase II [[clinical trial]]s between 2005 and 2008.<ref>{{ClinicalTrialsGov|NCT00267930|Study of RSD1235-SR for the Prevention of Atrial Fibrillation/Atrial Flutter Recurrence}}</ref><ref>{{ClinicalTrialsGov|NCT00526136|Vernakalant (Oral) Prevention of Atrial Fibrillation Recurrence Post-Conversion Study}}</ref>

==Mechanism of action==
Like other [[Antiarrhythmic agent#Class III agents|class III antiarrhythmics]], vernakalant blocks [[atrial]] [[potassium channel]]s, thereby prolonging repolarization. It differs from typical class III agents by blocking a certain type of potassium channel, the [[cardiac transient outward potassium current]], with increased potency as the [[heart rate]] increases. This means that it is more effective at high heart rates, while other class III agents tend to lose effectiveness under these circumstances. It also slightly blocks the [[hERG]] potassium channel, leading to a prolonged [[QT interval]]. This may theoretically increase the risk of [[ventricular tachycardia]], though this does not seem to be clinically relevant.<ref name="Finnin">{{cite |url=http://www.medscape.com/viewarticle/725628_4|title=Vernakalant: A Novel Agent for the Termination of Atrial Fibrillation: Pharmacology|publisher=Medscape Today|author=Miki Finnin|accessdate=12 October 2010}}</ref>

The drug also blocks atrial [[sodium channel]]s.<ref name="Finnin" />

==References==
{{reflist|2}}

{{Antiarrhythmic agents}}

[[Category:Antiarrhythmic agents]]
[[Category:Cardiovascular Drugs]]
[[Category:Drug]]