Differing Local Anaesthetic Potency and Toxicity of the Enantiomers of N‐n‐butyl‐3‐piperidyl 2′‐chloro‐6′‐methylcarbanilate: A New Local Anaesthetic

Abstract

Abstract: The R(+)‐form of N‐n‐butyl‐3‐piperidyl 2′‐chloro‐6′‐methylcarbanilate (HS 37) was a more potent local anaesthetic than the S(‐)‐form in various types of major nerve block, in infiltration anaesthesia and after topical application (guinea‐pigs, rabbits). The potency ratio varied with the method of administration and was between 2 and 3 in most of the tests. A similar difference in blocking activity was obtained in rate and equilibrium blocks of conduction in sheathed and de‐sheathed sciatic nerve (frogs). The effect of the racemate (infiltration, frog nerve) was intermediate to that of the enantiomers. The R(+)‐form was more toxic than the S(‐)‐form, both intravenously (mice, rabbits) and sub‐cutaneously (mice). Nerve blocking and toxic potencies of the enantiomers were positively correlated with ratios of about the same order of magnitude. The findings may indicate some stereo‐selectivity of action of the enantiomers in the excitable membranes rather than differences in concentration in the biophase.