Pharmacological studies of the enantiomer of bupivacaine

背景：左布比卡因和罗哌卡因都是单S(-)-对映体，比外消旋布比卡因具有更小的心脏毒性和惊厥作用。通过研究S(-)-布比卡因、R(+)-布比卡因和罗哌卡因对小龙虾巨轴突动作电位和dV/dt最大值（dV/dt max）的影响，直接比较了它们的体外麻醉作用。为了阐明细胞内麻醉浓度的差异，测定了细胞内电离麻醉浓度。方法：将脱毛小龙虾轴突分别灌注1 mM麻药，刺激频率分别为0.1 Hz和5 Hz。使用局部麻醉敏感微电极测量细胞内麻醉浓度。结果：在0.1 hz刺激下，两种模型均无差异。在5 Hz刺激下，小龙虾巨轴突的dV/dt max平均百分比下降的数量级为S(-)-布比卡因> R(+)-布比卡因>罗哌卡因。三种药物间细胞内局麻浓度无差异。结论：与罗哌卡因相比，S(-)-布比卡因对小龙虾巨轴突有较强的相位阻断作用。三种药物的细胞内等效局麻浓度表明细胞内质子化局麻浓度与阻断作用无直接关系。

Background : Levobupivacaine and ropivacaine are both single S(-)-enantiomers that have less cardiotoxic and convulsant effects than racemic bupivacaine. The anesthetic action of S(-)-bupivacaine, R(+)-bupivacaine and ropivacaine was directly compared in vitro by studying their effects on action potential and the maximum value of dV/dt (dV/dt max) in crayfish giant axon. To clarify the difference of intracellular anesthetic concentration, the intracellular ionized anesthetic concentration was measured.Methods : Desheathed crayfish axons were perfused with 1 mM of each anesthetic agent at a stimulation frequency of either 0.1 or 5 Hz. Intracellular anesthetic concentration was measured using local anesthetic-sensitive microelectrodes.Results : At 0.1-Hz stimulation, no differences were observed in either model. In crayfish giant axon at 5 Hz stimulation, the order of magnitude of the mean percentage decrease in dV/dt max was S(-)-bupivacaine > R(+)-bupivacaine> ropivacaine. Intracellular local anesthetic concentration did not differ among three agents.Conclusion : Compared with ropivacaine, S(-)-bupivacaine has potent phasic blocking effect in crayfish giant axon. The equivalent intracellular local anesthetic concentration among three agents suggests that intracellular protonated local anesthetic concentration are not directly correlated with blocking effects.