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.
D000200:Action Potentials / Q000187:drug effects; D000577:Amides / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004305:Dose-Response Relationship, Drug; D004952:Esters; D005041:Etidocaine / Q000494:pharmacology; D066298:In Vitro Techniques; D008012:Lidocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D008055:Lipids; D009412:Nerve Fibers / Q000187:drug effects; D009413:Nerve Fibers, Myelinated / Q000187:drug effects; D011817:Rabbits; D012995:Solubility; D013997:Time Factors; D014630:Vagus Nerve / Q000187:drug effects*
D000577:Amides; D000779:Anesthetics, Local; D004952:Esters; D008055:Lipids; C051685:2-(dimethylamino)-N-(2,6-dimethylphenyl)acetamide; D008012:Lidocaine; D005041:Etidocaine