The new antiarrhythmic substance AWD 23-111 inhibits the delayed rectifierpotassium current (IK) in guinea pig ventricular myocytes

The effects of N-(dicyclohexyl-carbamoylmethyl)-N-(3-diethylamino-propyl)-4 -nitro-benzamide hydrochloride (AWD 23-111), a novel antiarrhythmic compoun d, were studied in isolated cardiomyocytes of guinea pigs. Using whole-cell configuration of the patch-clamp technique AWD 23-111 was tested for its a bility to block the delayed rectifier potassium channel (IK). In guinea pig ventricular myocytes the current is composed of two components: IKr, a rap idly activating current and IKs, a slowly activating component which were d iscriminated by their different activation and deactivation behaviour. Ln t his preparation AWD 23-111 displayed concentration dependent inhibitory eff ects on IKr as well as on IKs in the tested concentration range between 1 a nd 100 mu mol/l. This blocking effect was independent of the stimulation fr equency (0.2, 1 and 2 Hz). There was no influence of AWD 23-111 on the ampl itude of L-type calcium whole-cell currents. The compound significantly pro longed action potential duration (APD) at a stimulation frequency of 2 Hz ( I and 10 mu mol/l). At 0.2 Hz then was no effect on APD. Our results sugges t that AWD 23-111 blocks both components of IK without a reverse use-depend ent effect on APD which limits the therapeutic potential of most other clas s III agents.