Section Review Central & Peripheral Nervous Systems: Prospects for the development of new volatile anaesthetics

Abstract

The mechanism of action of general anaesthetics is still unclear but a variety of evidence has strongly suggested that ion channels in the brain mediate some anaesthetic effects. The recent findings of stereoselective actions of volatile anaesthetics also indicate that a protein target is likely. Recent developments in anaesthetic mechanisms are discussed with particular emphasis on effects at GABA_A receptors. Despite recent improvements in anaesthetic care, perioperative morbidity remains a significant problem especially among the critically ill. Volatile anaesthetics remain in very wide use because of great experience with them and the ability to titrate their levels easily to achieve the desired actions. This extensive use is in spite of their significant side-effects of cardiovascular and respiratory depression. Volatile anaesthetics are among the most dangerous of drugs in clinical use and even modest improvements in their safety may have dramatic clinical ramifications. The limitations of current volatile anaesthetics are discussed in depth with reference to characteristics that would be desirable in a new drug. The potential of volatile anaesthetic stereoisomers as useful clinical drugs also remains a possibility if they show sufficient selectivity at sites mediating side-effects. Comparisons with intravenous agents are also made.