Development of newer calcium channel antagonists: therapeutic potential of efonidipine in preventing electrical remodelling during atrial fibrillation

Drugs. 2009;69(1):21-30. doi: 10.2165/00003495-200969010-00002.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / physiopathology
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, T-Type / drug effects
  • Dihydropyridines / pharmacology*
  • Drug Delivery Systems
  • Humans
  • Nitrophenols / pharmacology*
  • Organophosphorus Compounds / pharmacology

Substances

  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Calcium Channels, T-Type
  • Dihydropyridines
  • Nitrophenols
  • Organophosphorus Compounds
  • efonidipine