New local anesthetics with prolonged duration of action

本研究旨在开发新的局部麻醉剂，其作用时间比利多卡因更长，但效力相同。合成了三种侧链上含有甲酯(Li-Me)、乙酯(Li-Et)和丁酯(Li-Bu)的利多卡因衍生物。通过体外角膜反射抑制实验和迷走神经传导阻断实验，评价这些化合物的局部麻醉效应的起效时间和持续时间。去势迷走神经的平均传导阻断时间分别为32.5min(利多卡因)、39.9min(Li-Me)、68.2min(Li-ET)和108.7min(Li-Bu)，其中利多卡因和利多卡因酯类化合物之间的差异有统计学意义(Li-Ft和Li-Bu：P&lt；0.001)。这些化合物的持续时间延长可能是由于其理化性质(分配系数1.13，蛋白质结合力89%)所致。这些利多卡因酯的衍生物，特别是李布，是长效的局部麻醉药，可能对延长外科手术、疼痛诊所和野战阻滞有用。

The Present study was made to develop new local anesthetic agents which work longer than lidocaine and are equally potent. Three lidocaine derivatives structurally with methyl ester(Li-Me), ethyl ester(Li-Et), or butyl ester (Li-Bu) in the side chain were synthesized. Corneal reflex suppression and conduction blockade in the vagus nerve,in vitro, were examined to evaluate the onset and duration of the local anesthetic effect of these compounds. The mean conduction blockades in the removed vagus nerve lasted 32.5 min(lidocaine),39.9 min(Li-Me),68.2min(Li-Et),and 108.7min(Li-Bu) and the differences between the lidocaine and lidocaine ester derivatives were statistically significant (Li-Ft and Li-Bu:p<0.001). The prolonged effect of duration of these compounds may be due to physiochemical properties (partition coefficient 1.13, protein binding 89%). These lidocaine ester derivatives, especially Li-Bu, are long acting local anesthetics and may be useful for prolonged surgical procedures, pain clinics,and field block.