New lidocaine ester derivatives with a prolonged anesthetic effect.

In order to find a new long acting local anesthetic, methyl, ethyl, and butyl ester derivatives of lidocaine were synthesized in our laboratory. The topical anesthetic activity was studied with the effects on corneal reflex in rabbits, and the duration of action with those on the action potential of rabbit vagus nerve was studied in vitro. All drugs showed adequate topical anesthetic activities. The onset time to induce a complete blockage of the action potential in the excised vagus nerve was 97.1 +/- 6.3 s for lidocaine, 289.3 +/- 29.0 s for methyl ester, 186.3 +/- 18.4 s for ethyl ester, and 85.3 +/- 9.0 s for butyl ester. The mean duration of action, which was assessed as the time to recover from the complete block to 30% of control amplitude in a drug-free medium, was 32.5 +/- 3.1 min for lidocaine, 39.9 +/- 11.3 min for methyl ester, 68.2 +/- 4.2 min for ethyl ester, and 108.7 +/- 12.3 min for butyl ester. The differences in the duration of action between the ester derivatives and the original lidocaine were all statistically significant. The duration of action of all drugs studied paralleled with their protein binding capacities. These findings indicate the possibility that the ester derivatives studied, especially butyl ester, can be used as a long acting local anesthetic.