Pharmacological studies of the enantiomer of bupivacaine

背景资料：左旋布比卡因和罗哌卡因都是单一的S（-）-对映体，其心脏毒性和惊厥作用比外消旋布比卡因小。通过研究S（-）-布比卡因、R（+）-布比卡因和罗哌卡因对螯虾巨轴突动作电位和最大dV/dt（dV/dtmax）的影响，直接比较了它们的麻醉作用。为了澄清细胞内麻醉剂浓度的差异，细胞内离子化的麻醉剂concentrationweresmeasured. Methods：脱鞘的小龙虾轴突灌注与1 mM的每种麻醉剂在刺激频率为0.1或5 Hz。使用局部麻醉敏感的微电极测定细胞内麻醉药浓度。结果：在0.1 Hz的刺激，没有观察到任何模型中的差异。在5Hz电刺激下，小龙虾巨轴突的dV/dt max平均下降百分比的数量级顺序为S（-）-布比卡因> R（+）-布比卡因>罗哌卡因。结论：与罗哌卡因相比，S（-）-布比卡因对螯虾巨轴突有较强的时相阻滞作用。三种药物之间的等效细胞内局部麻醉药浓度表明细胞内质子化局部麻醉药浓度与阻滞效应不直接相关。

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.