Comparisons of the anesthetic potency and intracellular concentrations of S(-) and R(+) bupivacaine and ropivacaine in crayfish giant axon in vitro

Levobupivacaine and ropivacaine are both single S(-) enantiomers that have less severe cardiotoxic and convulsant effects than racemic bupivacaine. We compared the anesthetic actions of S(-) bupivacaine, R(+) bupivacaine, and ropivacaine in vitro by studying their effects on action potential amplitude and the maximal rate of rise of action potential in crayfish giant axon. To clarify the difference of intracellular anesthetic concentration, the intracellular ionized anesthetic concentration was measured. Desheathed crayfish axons were stimulated at a frequency of either 0.1 or 5 Hz and perfused with 1 mM of each anesthetic at pH 7.0. Intracellular anesthetic concentration was measured by using local anesthetic-sensitive glass microelectrodes. At 0.1-Hz stimulation, no differences were observed in their potency. At 5-Hz stimulation, the order of magnitude of the mean percentage decrease in maximal rate of rise of action potential was S(-) bupivacaine > R(+) bupivacaine > ropi-vacaine. Intracellular local anesthetic concentration did not differ among the three anesthetics at 0.1 Hz and 5 Hz. We conclude that, compared with ropivacaine, S(-) bupivacaine has a more potent phasic blocking effect in crayfish giant axon. The intracellular local anesthetic concentrations of S(-), R(+) bupivacaine and ropivacaine were not significantly different, regardless of differences in blocking effect and stimulation frequency. Implications: S(-) bupivacaine has a more potent phasic blocking effect than ropivacaine or R(+) bupivacaine in crayfish giant axons in vitro. An equivalent intracellular local anesthetic concentration for the three anesthetics was found, suggesting that the intracellular cationic local anesthetic concentration is not directly correlated with the intensity of block.