ANTIARRYHTHMIC DRUG ACTION ON VMAX OF CARDIAC CELLS

本次调查的目的是：(1)进一步检验 抗心律失常药物作用的调制受体假说 心脏钠通道。(2)开发更快、更完整的搜索 实验结果的分析方法，包括上下两部分 估计的限度。(3)结构-活性表征 利多卡因、普鲁卡因胺、阿普林丁和胺碘酮的关系 衍生品。(4)继续开发一种可以 电压钳制。(5)从调制的角度研究药物相互作用 受体假说。希望这项研究能进一步完善 我们对抗心律失常药物作用的理解； 阐明QSAR将促进更好、更安全的发展 抗心律失常药物；药物相互作用将提供更好的使用 目前可用的药物。 豚鼠乳头肌和单个分离的心肌细胞 电压钳制。将测量钠电流或Vmax，并且这些 数据将被用来估计药物堵塞的渠道。通过夹紧 准备不同的潜力和不同的持续时间是可能的 为了确定亲和力和相互作用的动力学 具有钠通道的抗心律失常药物。 经调制的受体常数及其生物物理性质 将使用聚类分析技术将药物关联起来，以揭开 定量构效关系(QSAR)。 定量构效关系的结果将用于改进现有的抗心律失常药物 并设计出新的。

The objectives of the present investigation are: (1) To further test the modulated receptor hypothesis for the action of antiarrhythmic drugs on cardiac sodium channels. (2) To develop a faster and more complete search method for analysis of the experimental results, including upper and lower limits for the estimates. (3) To characterize the structure-activity relationship for lidocaine procainamide, aprindine and amiodarone derivatives. (4) To continue the development of a preparation that can be voltage clamped. (5) To study drug interactions in terms of modulated receptor hypothesis. It is hoped that this research will further improve our understanding of the action of antiarrhythmic drugs; that the elucidation of the QSAR will promote the development of better and safer antiarrhythmic drugs; that the drug interactions will provide better use of the currently available drugs. Guinea pig papillary muscles and single isolated cardiocytes will be voltage clamped. The sodium current or Vmax will be measured and these data will be used to estimate the drug blocked channels. By clamping the preparations to various potentials and different durations it is possible to determine the affinity and the kinetics of the interaction of antiarrhythmic drugs with sodium channels. The modulated receptor constants and the biophysical properties of the drugs will be correlated using cluster analysis techniques to unravel the structure activity relationship in a quantitative fashion (QSAR). The results of QSAR will be used to improve existing antiarrhythmic drugs and to design new ones.