The in vitro sensitivities to local anaesthetic blockade of A, B and C nerve fibres in rabbit vagus nerves were examined using a series of structurally similar amino-ester agents which varied in lipid solubility and anaesthetic potency. A fibres were found to be the most sensitive and C fibres the least sensitive to conduction blockade with all the agents, provided that equilibrium blockade was allowed to develop. A correlation existed between the intrinsic anaesthetic potency of the various agents and their lipid solubilities. Equipotent concentrations of the drugs blocked C fibres at approximately the same rate, but there were marked variations in the rate at which A fibres were blocked. Amethocaine, an agent of high lipid solubility, blocked A fibres more quickly than C. As lipid solubility decreased through the series studied, so the onset of conduction blockade of A fibres was prolonged. It is suggested that this related to decreasing ability to penetrate the lipid diffusion barriers around A fibres. The traditional view that C fibres were more sensitive to block may have arisen because of confusion between absolute sensitivity and rate of development of conduction blockade.
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