Ion channel modulators as potential positive inotropic compound for treatment of heart failure

Clin Exp Pharmacol Physiol. 1994 Nov;21(11):833-43. doi: 10.1111/j.1440-1681.1994.tb02454.x.


1. Current positive inotropy therapy of heart failure is associated with major problems: digoxin and the phosphodiesterase inhibitors can cause life-threatening toxicity while beta-adrenoceptor agonists become less effective inotropic compounds as heart failure progresses. A new approach to positive inotropy is ion channel modulation. 2. An increased influx of Na+ during the cardiac action potential, as measured with DPI 201-106 and BDF 9148 which increase the probability of the open state of the Na+ channel, will increase force of contraction. 3. Activation of L-type Ca2+ channels with Bay K 8644 will increase influx of Ca2+ and increase the force of contraction. However the Ca2+ channel activators developed to date have little potential for the treatment of heart failure as they are vasoconstrictors. 4. Blocking cardiac K+ channels is a possible mechanism of positive inotropy. Terikalant inhibits the inward rectifying K+ channel, tedisamil inhibits the transient outward K+ channel and dofetilide is one of the newly developed inhibitors of the slow delayed outward rectifying K+ channel. All these drugs prolong the cardiac action potential to increase Ca2+ entry and force of contraction. 5. Thus drugs which increase Na+ influx or block K+ channels represent exciting possibilities for positive inotropy and the potential of these compounds for the treatment of heart failure needs to be fully evaluated.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium Channel Agonists / chemistry*
  • Calcium Channel Agonists / pharmacology
  • Cardiotonic Agents / chemistry*
  • Cardiotonic Agents / pharmacology
  • Dogs
  • Heart Failure / drug therapy*
  • Humans
  • Ion Exchange
  • Potassium Channel Blockers
  • Potassium Channels / agonists
  • Sodium Channel Agonists
  • Sodium Channel Blockers


  • Calcium Channel Agonists
  • Cardiotonic Agents
  • Potassium Channel Blockers
  • Potassium Channels
  • Sodium Channel Agonists
  • Sodium Channel Blockers