The neuronal lipid membrane permeability was markedly increased by bupivacaine and mildly affected by lidocaine and ropivacaine. 
We investigated the local anesthetic action on ionic membrane conductance (membrane conductance) and selectivity in membranes formed with neuronal phospholipids in the absence and presence of cholesterol.  In membranes without cholesterol, 1 mM bupivacaine and ropivacaine increased the membrane conductance approximately 4.5-fold; and 5 mM lidocaine, ropivacaine and bupivacaine increased the membrane conductance by 2.7-, 2.8- and 22.2-fold, respectively.  In the presence of cholesterol, 5 mM ropivacaine had no effect, lidocaine decreased the membrane conductance by 2-fold, and bupivacaine increased the membrane conductance by 17-fold.  Local anesthetics did not affect the ion selectivity in membranes without cholesterol, but they all decreased the Na(+) selectivity in membranes with cholesterol.  Cholesterol reduced the lidocaine- and ropivacaine-induced membrane conductance increase by eliminating or reversing the Na(+) conductance increase and by lowering the Cl(-) conductance increase.  In the absence of cholesterol, 5 mM bupivacaine increased both Na(+) conductance (38-fold) and Cl(-) conductance (19-fold), while in the presence of cholesterol it only increased Cl(-) conductance (26-fold).  Of the local anesthetics studied, ropivacaine was the least membrane toxic while bupivacaine was the most toxic.