Mazúr M, Stolc S, Horváth L I
Drugs Exp Clin Res. 1986;12(9-10):841-4.
Electrophysiological investigations of new drugs with carbanilate structure (heptacaine, carbisocaine) on axons and sciatic nerves of the rat have shown their high local anaesthetic effect at physiological pH. This effect is not only maintained at acid pH (6.0); it even increases on shifting pH from basic to acid values. To study this unique pH dependence of the effect of new local anaesthetics, drug-lipid interactions were investigated in liposomes prepared from egg yolk phosphatidylcholine or dimyristoyl phosphatidylcholine. The effect of the local anaesthetics on the molecular ordering of lipids in the liposomes was measured from spectral anisotropy of spin-labelled fatty acid incorporated in the membrane. It was concluded that the change of pH from 9.5 to 6.5 not only sustains the disordering effect of heptacaine and carbisocaine; it even potentiates it with the maximum disordering effect recorded at pH 6.5. This trend towards pH dependence in the effect of the new local anaesthetics is similar to that observed in biological preparations and is quite unlike the case of classic local anaesthetics (procaine, lidocaine). The possible mechanism of pH dependence is discussed.
对具有氨基甲酸酯结构的新药（庚卡因、卡比卡因）在大鼠轴突和坐骨神经上进行的电生理研究表明，它们在生理pH值下具有较高的局部麻醉作用。这种作用不仅在酸性pH值（6.0）时得以维持；当pH值从碱性转变为酸性时，其作用甚至增强。为了研究新型局部麻醉药作用这种独特的pH依赖性，在由蛋黄磷脂酰胆碱或二肉豆蔻酰磷脂酰胆碱制备的脂质体中研究了药物 - 脂质相互作用。通过掺入膜中的自旋标记脂肪酸的光谱各向异性来测量局部麻醉药对脂质体中脂质分子有序性的影响。得出的结论是，pH值从9.5变为6.5不仅维持了庚卡因和卡比卡因的无序化作用；甚至增强了这种作用，在pH 6.5时记录到最大无序化效果。新型局部麻醉药作用的这种pH依赖性趋势与在生物制剂中观察到的相似，并且与经典局部麻醉药（普鲁卡因、利多卡因）的情况大不相同。讨论了pH依赖性的可能机制。
