Stereoselective activity of local anesthetics

Most local anesthetic molecules contain an asymmetric carbon atom in their structure.Therefore, they provide excellent examples of chiral drugs that exist as two enantiomers, where each form may exhibit striking differences in its pharmacologic profile. Bupivacaine is currently marketed as a racemic mixture of both its S-(-)- and R-(+)-enantiomers. Fuelled by concerns about the cardiovascular toxicity of this preparation, research has focused on the pharmacology of the single enantiomers.The R-(+)-enantiomer has a higher potency as a sodium channel blocker than its “chiral twin” but correspondingly, also causes higher cardiovascular and central nervous system toxicity at lower doses.This work on bupivacaine has in turn driven the development and release of ropivacaine, an optically pure S-(-)-propyl homologue of bupivacaine.When compared with racemic bupivacaine, it demonstrates a significantly improved toxicity profile.This paper reviews some of the more recent literature on this subject in order to provide an account of current thinking on this important group of drugs.