Effects of 5-HT4 receptor agonist prokinetic agents on the action potential parameters of isolated rabbit myocardium

The effects of TS-951, a novel gastrointestinal prokinetic agent with 5-HT4 receptor agonistic action, on the action potential parameters of isolated rabbit Purkinje fiber, ventricular muscle and sinoatrial node, and on the s pontaneously beating rates of isolated rabbit right atria were compared wit h those of cisapride. TS-951 had no effect on the action potential paramete rs in both rabbit Purkinje fiber and ventricular muscle preparations. Howev er, cisapride significantly prolonged action potential duration (APD) in bo th preparations. Both TS-951 and cisapride produced a negative chronotropic effect in rabbit right atria; TS-951 and cisapride at 3 x 10(-5) mol/l red uced the beating rate by about 20 and 40%, respectively. In the sinoatrial node preparations, TS-951 (3 x 10(-5) mol/l) as well as cisapride (10(-6) m ol/l) prolonged cycle length and APD and reduced the diastolic depolarizati on rate. These results indicate that TS-951 does not appear to possess elec trophysiological features leading to cardiotoxicity such as QT prolongation and, thus, torsades de pointes in common with cisapride. Copyright (C) 200 1 S.Karger AG, Basel.