Development of newer calcium channel antagonists: therapeutic potential of efonidipine in preventing electrical remodelling during atrial fibrillation.
Calcium channel antagonists are most frequently prescribed for the treatment of hypertension and the majority specifically inhibit the L-type Ca2+ channel. In order to prevent reflex sympathetic over activity caused by L-type calcium channel antagonists (calcium channel blockers [CCBs]), increasing attention has focused on the blockade of the T-type Ca2+ channel. The T-type Ca2+ channel is found in the kidney and can also appear in the ventricle of the heart when in failure. Therefore, the T-type Ca2+ channel is a possible new target for the treatment of nephropathy and heart failure. In clinical trials, the efficacy and safety of T-type CCBs in hypertension and chronic renal disease have been reported. It is well known that the T-type Ca2+ channel is present in the adult atrium and plays a role in the cardiac pacemaker, but recent experimental studies suggest that this current also promotes electrical remodelling of the atrium. Using efonidipine, a dual L- and T-type CCB, it has been demonstrated that atrial electrical remodelling can be diminished in dogs. Furthermore, the T-type Ca2+ channel has recently been found in the pulmonary veins, contributing to the pulmonary vein pacemaker activity and triggered activity. A variety of drugs having T-type CCB effects have been shown to be effective in the management of atrial fibrillation, suggesting that this channel may be a novel therapeutic target.
Ohashi
Narutaka
N
Department of Medicine, Keio University School of Medicine, Tokyo, Japan. narutaka@cpnet.med.keio.ac.jp
Mitamura
Hideo
H
Ogawa
Satoshi
S
D000818:Animals; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D020747:Calcium Channels, T-Type / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology*; D016503:Drug Delivery Systems; D006801:Humans; D009596:Nitrophenols / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C066425:efonidipine