KC 12291: An Atypical Sodium Channel Blocker with Myocardial Antiischemic Properties

Gareth W. John, Robert Létienne, Bruno Le Grand, Christophe Pignier, Bernard Vacher, Jean Francois Patoiseau, Francis C. Colpaert, Alain Coulombe

Research output: Contribution to journalReview articlepeer-review

11 Scopus citations

Abstract

KC 12291 was designed as a voltage-gated sodium channel (VGSC) blocker with cardioprotective properties. KC 12291 has moderate inhibitory effects on peak (or rapid) Na+ current, and markedly reduces sustained (or slowly or non-inactivating) Na+ current. This distinguishes KC 12291 from conventional VGSC blockers such as local anesthetics or antiarrhythmics, which have little or no cardioprotective properties. Since VGSCs represent the main pathway for ischemic Na+ loading by failing to inactivate fully, KC 12291 exerts pronounced antiischemic activity principally by reducing the amplitude of sustained Na+ current. In isolated atria and Langendorff-perfused hearts, KC 12291 inhibits diastolic contracture, renowned for its resistance to pharmacological inhibition, reduces ischemic Na + loading and preserves cardiac energy status. KC 12291 exerts oral antiischemic activity in vivo in the absence of major hemodynamic effects. Cardiac VGSC blockers such as KC 12291, which block cardiac VGSCs in atypical fashion by effectively inhibiting the sustained component of Na+ current, represent, therefore, promising potential antiischemic and cardioprotective drugs.

Original languageEnglish
Pages (from-to)17-26
Number of pages10
JournalCardiovascular Drug Reviews
Volume22
Issue number1
DOIs
StatePublished - 2004
Externally publishedYes

Keywords

  • Calcium overload
  • Cardioprotection
  • KC 12291
  • Myocardial ischemia
  • Sodium channels
  • Sodium loading
  • Sustained Na current

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