• Br J Anaesth · Oct 1989

    Structure-activity relationships in differential nerve block at high and low frequency stimulation.

    • J A Wildsmith, D T Brown, D Paul, and S Johnson.
    • Department of Anaesthetics, Royal Infirmary, Edinburgh.
    • Br J Anaesth. 1989 Oct 1;63(4):444-52.

    AbstractWe have examined the in vitro sensitivities of A, B and C fibres in rabbit vagus nerves to local anaesthetic block with a range of local anaesthetic drugs. The nerves were maintained at 37 degrees C and pH 7.4 using an electrolyte solution equilibrated with 5% carbon dioxide. A fibres were the most, and C fibres the least, sensitive to block at low frequency stimulation (0.0167 Hz). Equipotent concentrations of the various drugs blocked C fibres at approximately the same rate. Rate of A fibre block was related to physicochemical properties of individual drugs. Low pKa and high lipid solubility favoured block of A fibres before C, whereas the reverse was true for high pKa and low solubility. Absolute potency was related to lipid solubility, but each type of local anaesthetic drug in clinical use has a different inherent potency. With stimulation at high frequencies (20 and 40 Hz), C fibres were more sensitive to use-dependent block than A fibres; this effect was more marked with drugs containing an amide than an ester linkage. Molecular size and lipid solubility may inter-react to govern the ability to produce use dependent block. Agents which contain an amide linking group, have a high pKa and are of low lipid solubility, may be used to produce differential C fibre block.

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