Flesch M, Erdmann E
Klinik III für Innere Medizin der Universität zu Köln, Germany.
Cardiovasc Drugs Ther. 2001 Sep;15(5):379-86. doi: 10.1023/a:1013329203750.
The Na+ channel agonists DPI 201-106, BDF 9148 and BDF 9198 are a new group of positive inotropic agents which increase cardiac contractility in a cAMP independent manner. The most likely mechanism by which positive inotropy is mediated is an enhancement of Na+/Ca2+ exchange activity in response to a Na+ channel agonist induced increase in the cardiac myocyte intracellular Na+ concentration. While the positive inotropic effect of drugs which exert their effects in a cAMP dependent manner is blunted in failing compared to nonfailing myocardium, the efficacy and potency of Na+ channel agonists is not only maintained, but enhanced in failing myocardium. This finding makes these substances interesting for the treatment of patients with heart failure. The positive inotropic effects of the Na+ channel agonists, however, are accompanied by a potential increase in the incidence of cardiac arrhythmias. These side effects might limit the clinical use of Na+ channel agonists and demand future development of Na+ channel modulators without significant arrhythmogenic effects.
钠离子通道激动剂DPI 201 - 106、BDF 9148和BDF 9198是一类新型正性肌力药物，它们以不依赖环磷酸腺苷（cAMP）的方式增强心肌收缩力。介导正性肌力作用最可能的机制是，响应钠离子通道激动剂诱导的心肌细胞内钠离子浓度升高，增强钠/钙交换活性。与非衰竭心肌相比，以依赖cAMP方式发挥作用的药物在衰竭心肌中的正性肌力作用减弱，而钠离子通道激动剂的疗效和效能不仅得以维持，在衰竭心肌中还会增强。这一发现使得这些物质在治疗心力衰竭患者方面具有吸引力。然而，钠离子通道激动剂的正性肌力作用伴随着心律失常发生率的潜在增加。这些副作用可能会限制钠离子通道激动剂的临床应用，并需要未来开发无明显致心律失常作用的钠离子通道调节剂。
