Membrane effects of ropivacaine compared with those of bupivacaine and mepivacaine.

We compared the effects of ropivacaine, bupivacaine and mepivacaine on membrane lipids in an attempt to determine the anaesthetic mechanism of ropivacaine with structure-dependent potency. The membrane effects were determined by measuring anaesthetic-induced changes in the phase transition temperature and the fluorescence polarization of liposomal membranes prepared with cholesterol and phosphatidylcholine. Bupivacaine, ropivacaine and mepivacaine depressed the membrane lipid phase transition and decreased the polarization of liposomal membranes at 0.0625-1.0 mg/mL, indicating that these anaesthetics fluidize membranes at concentrations lower than those in clinical use. Ropivacaine and bupivacaine were effective in fluidizing the membrane core rather than the membrane surface, whereas mepivacaine was a membrane fluidizer acting equally on both regions. In the comparison of membrane fluidization at an equimolar concentration (3.0 mmol/L), ropivacaine was found to be less potent than bupivacaine and more potent than mepivacaine. This membrane-fluidizing potency was also consistent with the hydrophobic properties of these substances evaluated by reversed-phase chromatography. Structure-dependent membrane fluidization associating with hydrophobicity appears to underlie the local anaesthetic effect of ropivacaine as well as those of bupivacaine and mepivacaine.