Vernakalant

Vernakalant

Systematic (IUPAC) name
(3R)-1-{(1R,2R)-2-[2-(3,4-dimethoxyphenyl) ethoxy]cyclohexyl}pyrrolidin-3-ol
Clinical data
Licence data	EMA:Link
Legal status	℞ (Prescription only)
Routes of administration	Intravenous, oral
Identifiers
CAS Number	794466-70-9 Y Template:CAS (HCl)
ATC code	C01BG11 (WHO)
PubChem	CID: 9930049
ChemSpider	8105680 N
UNII	9G468C8B13 Y
Chemical data
Formula	C20H31NO4
Molecular mass	349.464 g/mol
SMILES O(c1ccc(cc1OC)CCO[C@@H]3CCCC[C@H]3N2CC[C@@H](O)C2)C
InChI InChI=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 N Key:VBHQKCBVWWUUKN-KZNAEPCWSA-N N
NY (what is this?)  (verify)

Vernakalant (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 was bought for further development by Merck in April 2009. In September 2012, Merck terminated its agreements with Cardiome and has consequently returned all rights of the drug back to Cardiome.

On 11 December 2007, the Cardiovascular and Renal Drugs Advisory Committee of the US Food and Drug Administration (FDA) voted to recommend the approval of vernakalant, but in August 2008 the FDA judged that additional information was necessary for approval. The drug (under brand name Brinavess) was approved in Europe on 1 September 2010.

An oral formulation underwent Phase II clinical trials between 2005 and 2008.

Mechanism of action

Like other class III antiarrhythmics, vernakalant blocks atrial potassium channels, 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.

The drug also blocks atrial sodium channels.