Mechanism of action of general anaesthetic drugs

Abstract 

The mechanism by which drugs can cause a reversible loss of consciousness is still the subject of intense debate. An enduring finding has been that lipid solubility correlates with anaesthetic potency, indicating a lipophilic site of action. Suitable sites are the cell membrane bilayer and the proteins imbedded in it. All anaesthetics can affect voltage-gated ion channels, but in general these effects occur at greater concentrations than those necessary to produce anaesthesia. Neurotransmitter receptors, particularly the ligand-gated ion channels, are particularly sensitive to anaesthetic agents. Attention is drawn to the receptors activated by the excitatory amino acids as ketamine blocks the channel of the N-methyl-d-aspartate (NMDA) receptor. However, many anaesthetics enhance inhibitory transmission via the γ-aminobutyric acid A (GABA_A) receptor, although the binding site that mediates this effect varies for individual agents. Recent evidence suggests that some separation between the wanted and unwanted effects of anaesthetics may be possible.

Keywords: GABA_A receptors, ligand-gated ion channels, membrane fluidization, NMDA receptors, voltage-gated ion channels