New insights into the molecular mechanisms of general anaesthetics

• Published in: British journal of pharmacology Vol. 161; no. 2; pp. 288 - 307
• Main Author: Chau, P‐L
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2010; Nature Publishing Group
• Subjects: Anesthetics, General - adverse effects; Anesthetics, General - chemistry; Anesthetics, General - pharmacology; Animals; Biological and medical sciences; Biomedical Research - methods; Biomedical Research - trends; Brain; Brain - drug effects; Brain - metabolism; GABA receptor; general anaesthetics; glycine receptor; Humans; Medical sciences; membrane; Models, Molecular; Molecular Structure; NMDA receptor; Pharmacology. Drug treatments; Point Mutation; pressure reversal; Protein Binding; Receptors, GABA-A - chemistry; Receptors, GABA-A - genetics; Receptors, GABA-A - metabolism; Receptors, N-Methyl-D-Aspartate - chemistry; Receptors, N-Methyl-D-Aspartate - genetics; Receptors, N-Methyl-D-Aspartate - metabolism; Reviews; Stereoisomerism; Structure-Activity Relationship; Gabaergic receptor; membrane; General anesthetic; Glycine receptor; Reversibility; GABA receptor; pressure reversal; Glutamate receptor; Mechanism of action; NMDA receptor; general anaesthetics
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.2010.00891.x

This paper provides new insights of how general anaesthetic research should be carried out in the future by an analysis of what we know, what we do not know and what we would like to know. I describe previous hypotheses on the mechanism of action of general anaesthetics (GAs) involving membranes and protein receptors. I provide the reasons why the GABA type A receptor, the NMDA receptor and the glycine receptor are strong candidates for the sites of action of GAs. I follow with a review on attempts to provide a mechanism of action, and how future research should be conducted with the help of physical and chemical methods.