Carvedilol and vesnarinone: new antiarrhythmic approach in heart failure therapy.
Carvedilol and vesnarinone are drugs attracting recent interest in the treatment of chronic heart failure. Electrophysiologic studies have revealed that these drugs cause a moderate prolongation of action potential duration (APD) of ventricular muscles with minimal "reverse frequency-dependence" through different ionic mechanisms. Carvedilol blocks L-type Ca2+ current (ICa), transient outward K+ current (Ito), and delayed rectifier K+ current (IK) preferentially for the rapidly activating component (IKr). Vesnarinone is a selective blocker of IK with a unique drug-channel interaction. From the voltage- and time-dependence of IK inhibition, vesnarinone is considered to bind the IK (mainly IKr) channel during the activated state and unbind during the closed state. These electropharmacologic profiles provide a new approach for the development of an ideal antiarrhythmic drugs in patients with structural heart diseases.
Cheng
J H
JH
School of Life Science and Medical Engineering, Tongji University, Shanghai 200092, China. dewang@online.sh.cn
Kamiya
K
K
Kodama
I
I
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D000077261:Carvedilol; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D015221:Potassium Channels / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*; D011719:Pyrazines; D011804:Quinolines / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D020746:Calcium Channels, L-Type; D002227:Carbazoles; D002316:Cardiotonic Agents; D015221:Potassium Channels; D011412:Propanolamines; D011719:Pyrazines; D011804:Quinolines; D000077261:Carvedilol; C041667:vesnarinone