ELECTROPHYSIOLOGICAL EFFECTS OF EGIS-7229, A NEW ANTIARRHYTHMIC AGENT, IN ISOLATED GUINEA-PIG PAPILLARY-MUSCLE

1. The cellular electrophysiological effects of EGIS-7229, a novel ant iarrhythmic agent, were studied in guinea pig papillary muscles with t he use of conventional microelectrode techniques. 2. The drug had a co ncentration-dependent biphasic effect on action potential duration (AP D). APD was significantly lengthened at low concentration (3 mu mol/l) , whereas it was shortened at concentrations higher than 10 mu mol/l. 3. At concentrations higher than 10 mu mol/l, the drug decreased the m aximum velocity of action potential upstroke (V-max), the force of con traction, and altered the restitution kinetics of APD. 4. The effect o f EGIS-7229 on V-max was frequency 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 II I characteristics, Class III properties are present at low concentrati ons, whereas, at higher concentrations, class I actions may be predomi nant. GEN PHARMAC 29;2:275-280, 1997. (C) 1997 Elsevier Science Inc.