GENETIC-DIFFERENCES AFFECTING THE POTENCY OF STEREOISOMERS OF ISOFLURANE

Background: In previous studies, researchers demonstrated the ability of a variety of organisms and in vitro sites of anesthetic action to d istinguish between stereoisomers of isoflurane or halothane. However, it was not shown whether organisms with differing sensitivities to ste reoisomers of one volatile anesthetic are able to distinguish between stereoisomers of another. In this study, the responses of mutants of C aenorbabditis elegans to stereoisomers of isoflurane were determined f or comparison to previous results in halothane. Methods: Mutant strain s of C. elegans were isolated and grown by standard techniques. The EC (50)s (the effective concentrations of anesthetia at which 50% of the animals are immobilized for 10 s) of stereoisomers of isoflurane and t he racemate were determined in wild type and mutant strains of C. eleg ans. Results: Wild type C. elegans and strains with high EC(50)s of th e racemate were more sensitive to the (+) isomer of isoflurane by appr oximately 30%. The racemate showed a EC(50)s similar to the less poten t isomer, the (-) form. In the strains with low EC(50)s, one strain sh owed no ability to differentiate between the stereoisomers, whereas tw o showed a 60% difference between the (+) and (-) forms. Conclusions: The ability to distinguish between stereoisomers of isoflurane is asso ciated with genetic loci separate from those that distinguish between stereoisomers of halothane. These results are consistent with multiple sites of action for these anesthetics.