Effect of local anaesthetics and pH: new aspects

The pH dependence of the effect of local anaesthetics with ester, amide, or carbanilate structure on action potential conduction was studied in rat desheathed sciatic nerve and in single axon preparation in vitro. Not only different slopes but also different directions of this dependence were observed in the pH range 6.0-8.4. The effect of common local anaesthetics such as procaine, lidocaine, trimecaine, and bupivacaine kept decreasing with lower pH. New drugs with carbanilate structure, however (pentacaine, carbisocaine and heptacaine) displayed an opposite dependence. Further analysis showed that this phenomenon cannot be linked to the type of the intermediary chain of the drugs, to differences in pKa values, or to differences in potency of the drugs. Yet a relationship was found to exist between pH dependence and the lipophilicity of the drug. It is suggested that the current hypothesis concerning the pH dependence of the effect of local anaesthetics be complemented by the lipophilic properties of such drugs. This implies a pH dependent formation of micelles in highly lipophilic local anaesthetics which changes their bioavailability, as well as a diffusion of these drugs into and through the lipoid phase besides the base also in the form of an ion pair.