Electrophysiological effects of EGIS-7229, a new antiarrhythmic agent, in isolated guinea pig papillary muscle

Gen Pharmacol. 1997 Aug;29(2):275-80. doi: 10.1016/s0306-3623(96)00461-2.

Abstract

1. The cellular electrphysiological effects of EGIS-7229, a novel antiarrhythmic agent, were studied in guinea pig papillary muscles with the use of conventional microelectrode techniques. 2. The drug had a concentration-dependent biphasic effect on action potential duration (APD). APD was significantly lengthened at low concentration (3 mumol/1), whereas it was shortened at concentrations higher than 10 mumol/l. 3. At concentrations higher than 10 mumol/l, the drug decreased the maximum velocity of action potential upstroke (Vmax), the force contraction, and altered the restitution kinetics of APD. 4. The effect of EGIS-7229 on Vmax was frequently dependent; it was most prominent at short pacing cycle lengths (use-dependent block). 5. On the basis of present results, EGIS-7229 appears to carry mixed class I and class III characteristics. Class III properties are present at low concentrations, whereas, at higher concentrations, class I actions may be predominant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects*
  • Animals
  • Anti-Arrhythmia Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • In Vitro Techniques
  • Papillary Muscles / drug effects*
  • Papillary Muscles / physiology
  • Pyridazines / pharmacology*

Substances

  • Anti-Arrhythmia Agents
  • EGIS 7229
  • Pyridazines