Klapperstück M, Markwardt F
Julius-Bernstein-Institute for Physiology, Martin-Luther-University Halle Wittenberg, Saale, Germany.
Pharmazie. 1999 Jan;54(1):61-8.
The effects of N-(dicyclohexyl-carbamoylmethyl)-N-(3-diethylamino-propyl)-4-nitro -benzamide hydrochloride (AWD 23-111), a novel antiarrhythmic compound, were studied in isolated cardiomyocytes of guinea pigs. Using whole-cell configuration of the patch-clamp technique AWD 23-111 was tested for its ability to block the delayed rectifier potassium channel (IK). In guinea pig ventricular myocytes the current is composed of two components: IKr, a rapidly activating current and IKs, a slowly activating component which were discriminated by their different activation and deactivation behaviour. In this preparation AWD 23-111 displayed concentration dependent inhibitory effects on IKr as well as on IKs in the tested concentration range between 1 and 100 mumol/l. This blocking effect was independent of the stimulation frequency (0.2, 1 and 2 Hz). There was no influence of AWD 23-111 on the amplitude of L-type calcium whole-cell currents. The compound significantly prolonged action potential duration (APD) at a stimulation frequency of 2 Hz (1 and 10 mumol/l). At 0.2 Hz there was no effect on APD. Our results suggest that AWD 23-111 blocks both components of IK without a reverse use-dependent effect on APD which limits the therapeutic potential of most other class III agents.
研究了新型抗心律失常化合物N-（二环己基-氨基甲酰甲基）-N-（3-二乙氨基丙基）-4-硝基苯甲酰胺盐酸盐（AWD 23-111）对豚鼠离体心肌细胞的作用。采用膜片钳技术的全细胞模式，检测AWD 23-111阻断延迟整流钾通道（IK）的能力。在豚鼠心室肌细胞中，该电流由两个成分组成：IKr，一种快速激活电流；IKs，一种缓慢激活成分，可通过它们不同的激活和失活行为来区分。在该制剂中，在1至100μmol/l的测试浓度范围内，AWD 23-111对IKr以及IKs均表现出浓度依赖性抑制作用。这种阻断作用与刺激频率（0.2、1和2Hz）无关。AWD 23-111对L型钙全细胞电流的幅度没有影响。在2Hz的刺激频率下（1和10μmol/l），该化合物显著延长动作电位时程（APD）。在0.2Hz时，对APD没有影响。我们的结果表明，AWD 23-111阻断IK的两个成分，且对APD没有反向使用依赖性效应，这限制了大多数其他III类药物的治疗潜力。
