A unitary theory of general anaesthesia has been sought for many years without success. The current consensus is that inhalation anaesthetics bind to the lipophilic residues of various ligand gated receptor proteins, particularly GABAA. They potentiate the effects of GABA with the end result that neuronal activity is decreased, in the same way as with most injection anaesthetics. However, inhalation anaesthetics also have lots of other effects which may be clinically important. An inhibitory effect at neuronal nAChR may be important. Nitrous oxide and xenon preferentially target the NMDA receptor (cf ketamine).
Most injectable drugs bind to GABAA receptors to facilitate channel opening, and thus hyperpolarise neurones. This produces generalised inhibition of neurones, but may also produce excitory effects through disinhibition. Many anaesthetics also have other effects of unknown importance (effects on other receptors and non specific effects). Ketamine is an NMDA receptor channel blocker and is thought to produce its effects by this mechanism.
An endogenous ligand, oleamide, has recently been discovered for the general anaesthetic binding site on the GABA receptor. This may mean that specific agonists and antagonists will be available some time in the future.
