Mechanisms of action of general anaesthetic drugs

Abstract

Based on the diverse array of anaesthetic structures, a single anaesthetic target site seems unlikely. With the knowledge that anaesthesia likely results from central nervous system depression, it can be hypothesized that anaesthesia results from either enhanced inhibitory transmission or reduced excitatory transmission. Two main targets have been extensively described: GABAA receptors and N-methyl-d-aspartate (NMDA) glutamate receptors. On γ-aminobutyric acid (GABA) binding to GABAA receptors, an influx of Cl− results to produce hyperpolarization. With the exception of ketamine, xenon and nitrous oxide, all anaesthetic agents potentiate GABA-mediated conductance. On binding of the main excitatory transmitter glutamate, NMDA receptors gate an influx of Ca2+ and Na+. Ketamine, xenon and nitrous oxide inhibit this ion movement to depress excitatory transmission.