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The potential for safer anaesthesia using stereoselective anaesthetics
E J Moody1, B D Harris, P Skolnick
1Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, Baltimore MD 21287.
Trends in Pharmacological Sciences
|October 1, 1994
Summary
The molecular targets of anesthetics are likely proteins, not lipids. This is evidenced by differing potencies of isoflurane isomers, suggesting potential for improved anesthetic agents.
Area of Science:
- Anesthesiology and Pharmacology
- Molecular Biology
- Stereochemistry
Background:
- The precise molecular mechanisms underlying inhalational anesthesia remain debated despite extensive clinical application.
- Understanding these mechanisms is crucial for developing safer and more effective anesthetic agents.
Purpose of the Study:
- To investigate the role of proteins versus lipids as the primary targets of volatile anesthetic action.
- To explore the potential clinical utility of stereoselective anesthetic agents.
Main Methods:
- Comparison of the anesthetic potencies of the optically active isomers of isoflurane ((+)- and (-)-isoflurane).
- Assessment of the stereoselectivity of myocardial suppression by isoflurane isomers.
Main Results:
- A significant difference in anesthetic potencies was observed between (+)- and (-)-isoflurane.
- Myocardial suppression by isoflurane isomers showed a lack of stereoselectivity.
- These findings support protein as the primary target for anesthetic action.
Conclusions:
- The stereoselectivity in anesthetic potency, but not in myocardial suppression, strongly suggests proteins are key anesthetic targets.
- Optically active volatile anesthetics offer novel tools for elucidating anesthetic mechanisms.
- Stereoselective volatile agents may provide clinical advantages over current racemic mixtures.