A pH-dependent disordering efficacy of new local anaesthetics with carbanilate structure. A spin label study in model...

Electrophysiological investigations of new drugs with carbanilate structure (heptacaine, carbisocaine) on axons and sciatic nerves of the rat have shown their high local anaesthetic effect at physiological pH. This effect is not only maintained at acid pH (6.0); it even increases on shifting pH from basic to acid values. To study this unique pH dependence of the effect of new local anaesthetics, drug-lipid interactions were investigated in liposomes prepared from egg yolk phosphatidylcholine or dimyristoyl phosphatidylcholine. The effect of the local anaesthetics on the molecular ordering of lipids in the liposomes was measured from spectral anisotropy of spin-labelled fatty acid incorporated in the membrane. It was concluded that the change of pH from 9.5 to 6.5 not only sustains the disordering effect of heptacaine and carbisocaine; it even potentiates it with the maximum disordering effect recorded at pH 6.5. This trend towards pH dependence in the effect of the new local anaesthetics is similar to that observed in biological preparations and is quite unlike the case of classic local anaesthetics (procaine, lidocaine). The possible mechanism of pH dependence is discussed.