Manabe A, Shirasaki K, Kawashima I, Nakayama S, Kasahara T, Sakamoto K
Nihon Yakurigaku Zasshi. 1985 Jul;86(1):41-9. doi: 10.1254/fpj.86.41.
The effects of antiarrhythmic drugs, aprindine, mexiletine and lidocaine, on rat erythrocytes, isolated rat hepatocytes and DPPC-liposomes were studied at various concentrations. Maximal inhibition of aprindine on the hypotonic hemolysis was observed at a concentration of 2 X 10(-4) M. In isolated rat hepatocytes, aprindine caused an increase in GOT leakage above 4 X 10(-4) M. Mexiletine and lidocaine caused a slight decrease in GOT. Only aprindine caused an increase in LDH leakage above 2 X 10(-4) M. In the relationship between the surface tension and pH conditions (pH 5.7, 7.4 and 8.0), aprindine and mexiletine indicated a depression of surface tension at a dose of 10(-4) M to 10(-3) M under all pH conditions. Lidocaine indicated a depression of surface tension at a dose of 10(-4) M at pH 8.0 only. Aprindine and mexiletine depressed the phase transition temperature (Tc) of DPPC-liposomes. The depression of Tc by aprindine was greater than that by mexiletine. The rank by order of surface activity was the same as that of enzyme leakage from hepatocytes, hemolysis of erythrocytes and depression of Tc in DPPC-liposomes in vitro. These results suggest that differences in membrane damage produced by antiarrhythmic drugs may by related to surface activity, which in turn may determine the extent of adsorption onto cell membranes.
研究了抗心律失常药物安搏律定、美西律和利多卡因在不同浓度下对大鼠红细胞、离体大鼠肝细胞和二棕榈酰磷脂酰胆碱（DPPC）脂质体的影响。观察到安搏律定在浓度为2×10⁻⁴M时对低渗溶血的抑制作用最大。在离体大鼠肝细胞中，安搏律定在浓度高于4×10⁻⁴M时导致谷草转氨酶（GOT）泄漏增加。美西律和利多卡因使GOT略有下降。只有安搏律定在浓度高于2×10⁻⁴M时导致乳酸脱氢酶（LDH）泄漏增加。在表面张力与pH条件（pH 5.7、7.4和8.0）的关系中，在所有pH条件下，安搏律定和美西律在剂量为10⁻⁴M至10⁻³M时均表现出表面张力降低。利多卡因仅在pH 8.0时剂量为10⁻⁴M时表现出表面张力降低。安搏律定和美西律降低了DPPC脂质体的相变温度（Tc）。安搏律定对Tc的降低作用大于美西律。体外表面活性的顺序与肝细胞酶泄漏、红细胞溶血以及DPPC脂质体中Tc降低的顺序相同。这些结果表明，抗心律失常药物产生的膜损伤差异可能与表面活性有关，而表面活性反过来可能决定其在细胞膜上的吸附程度。
