Vernakalant
Encyclopedia
Vernakalant 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
in April 2009.
On December 11, 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 was approved in Europe on September 1, 2010.
An oral formulation underwent Phase II clinical trial
s between 2005 and 2008.
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.
The drug also blocks atrial sodium channels.
Atrial fibrillation
Atrial fibrillation is the most common cardiac arrhythmia . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving coordinated contraction...
. It was initially developed by Cardiome Pharma, and the intravenous formulation has been bought for further development by Merck
Merck & Co.
Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...
in April 2009.
On December 11, 2007, the Cardiovascular and Renal Drugs Advisory Committee of the US
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) voted to recommend the approval of vernakalant, but in August 2008 the FDA judged that additional information was necessary for approval.
The drug was approved in Europe on September 1, 2010.
An oral formulation underwent Phase II clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s between 2005 and 2008.
Mechanism of action
Like other class III antiarrhythmics, vernakalant blocks atrial potassium channelPotassium channel
In the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes...
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
Cardiac transient outward potassium current
The cardiac transient outward potassium current is the main contributing current to the repolarizing phase 1 of the cardiac action potential, and results from movement of potassium ions from the intracellular to the extracellular space...
, with increased potency as the heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....
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
HERG
hERG is a gene that codes for a protein known as Kv11.1 potassium ion channel...
potassium channel, leading to a prolonged QT interval
QT interval
In cardiology, the QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. In general, the QT interval represents electrical depolarization and repolarization of the left and right ventricles...
. This may theoretically increase the risk of ventricular tachycardia
Ventricular tachycardia
Ventricular tachycardia is a tachycardia, or fast heart rhythm, that originates in one of the ventricles of the heart...
, though this does not seem to be clinically relevant.
The drug also blocks atrial sodium channels.