Differential nerve blockade: esters v. amides and the influence of pKa

The in vitro sensitivities to local anaesthetic blockade of A, B and C fibres in rabbit vagus nerves were examined using a series of structurally similar amide agents, which varied in lipid solubility and anaesthetic potency. The actions of these drugs were compared with one another, and with those of a series of amino-ester local anaesthetics studied previously. The results demonstrated that A fibres are the most, and C fibres the least, sensitive to blockade by local anaesthetic agents. As with the ester drugs, equipotent concentrations of the amides blocked C fibres at approximately the same rate, but the absolute and relative rates of development of A fibre blockade were related to lipid solubility. As the latter increased, so did the rate of A fibre blockade. Combining the results of the two studies suggests that an agent of low lipid solubility and high pKa might be used to produce differential C fibre blockade. Comparison of the results obtained with the two different classes of drug indicates that the ester structure may have an inherently more potent action than the amide.