Toxicological and Local Anaesthetic Effects of Optically Active Isomers of Two Local Anaesthetic Compounds

Abstract

Mepivacaine: There was no difference in toxicity between the two optical isomers of mepivacaine after rapid intravenous injections into mice or rats. After slow intravenous injections or after subcutaneous injections the L(+)– isomer however was less toxic than the D(‐) – isomer. This might at least partly be explained by the results obtained from other experiments, which demonstrated that after slow infusions of the drugs into rabbits more L(+)–mepivacaine than D(‐)–mepivacaine was taken up by the lungs, thus reducing the concentration of the drug reaching the brain, where significantly more D(‐)– mepivacaine than L(+)–mepivacaine was found. A slow absorption of L(+)–mepivacaine in comparison with D(‐)–mepivacaine from the site of injection is demonstrated and might contribute to the differences in subcutaneous toxicity and might also be the cause of the significantly longer duration of infiltration anaesthesia by the L(+)–isomer than by the D(‐)–isomer, since the same nerve‐blocking effect of the isomers was found in vitro. Bupivacaine: There were significant differences between the toxicity of the bupivacaine isomers when given intravenously and subcutaneously; the D(+)–isomer was more toxic. This as well as the very long duration of infiltration anaesthesia by L(‐)–bupivacaine indicate differences in absorption rates between the bupivacaine isomers similar to those demonstrated for the mepivacaine isomers.