Stereochemistry in anaesthesia

Abstract

1. Interest in the pharmacokinetic and pharmacodynamic properties of the enantiomers of chiral drugs has greatly increased in recent years. This is particularly so for agents used in anaesthesia. 2. Chiral compounds are those that can exist in two nonsuperimposable forms. Each form is termed an enantiomer or stereoisomer. Two naming systems are in use: one uses the terms (+) and (-) to indicate the direction the compound will rotate polarized light, while the other system, based on the absolute three-dimensional structure of the enantiomers, uses the terms R and S. 3. Investigation of the stereoisomers of the volatile anaesthetic agent isoflurane is increasing our understanding of the mechanism of general anaesthesia. Current evidence suggests a protein, rather than a lipid, receptor site. 4. Investigation of the stereoisomers of local anaesthetics is increasing the safety of these drugs. 5. For bupivacaine, a widely used amide local anaesthetic, important enantiomeric differences can be found for toxicity, clinical effect and pharmacokinetics. In particular S-(-)-bupivacaine has an improved central nervous system and cardiac safety profile. This is partly explained by the pharmacokinetic differences. 6. Based on these differences, ropivacaine, a propyl homologue of bupivacaine, has been produced solely as the S-(-)-enantiomer. The available evidence suggests significantly improved safety for this agent over racemic bupivacaine.