Himmel H M, Wilhelm D, Ravens U
Pharmakologisches Institut, Universität-Gesamthochschule Essen, F.R.G.
Eur J Pharmacol. 1990 Oct 9;187(2):235-40. doi: 10.1016/0014-2999(90)90010-4.
In isolated heart muscle, the compound R56865 (N-[1-[4-(4-fluorophenoxy)butyl]-4-piperidinyl]-N-methyl-2- benzothiazolamine) has been shown to protect against intoxication by cardiac glycosides. We studied the influence of R56865 on various membrane currents in single isolated ventricular cardiomyocytes of the guinea-pig. The sodium current, INa, was investigated at reduced extracellular Na+ (30 mM) in the presence of Cd2+ to block the calcium current, ICa, and with Cs+ substituted for K+ to reduce the K+ currents, IK. Under these conditions, R56865 concentration dependently decreased the peak INa with a half-maximum effect at about 1 microM. The steady state inactivation and normalized conductance of INa were not significantly different from the control. In 'normal' Tyrode solution, R56865 (10 microM) did not markedly reduce ICa, and did not affect the quasi steady state IK, which was taken as an index of K+ conductance. We conclude that R56865 possesses Na+ channel-blocking properties, whereas ICa and membrane K+ conductance were not influenced.
在离体心肌中，化合物R56865（N-[1-[4-(4-氟苯氧基)丁基]-4-哌啶基]-N-甲基-2-苯并噻唑胺）已被证明可防止强心苷中毒。我们研究了R56865对豚鼠单个离体心室肌细胞中各种膜电流的影响。在存在Cd2+以阻断钙电流ICa且用Cs+替代K+以减少钾电流IK的情况下，于降低的细胞外Na+（30 mM）浓度下研究钠电流INa。在这些条件下，R56865浓度依赖性地降低了峰值INa，在约1 microM时具有半数最大效应。INa的稳态失活和标准化电导与对照组无显著差异。在“正常”的台氏液中，R56865（10 microM）并未显著降低ICa，也未影响作为钾电导指标的准稳态IK。我们得出结论，R56865具有钠通道阻断特性，而ICa和膜钾电导未受影响。
