[Effects of intravenous anesthetics on neurons of the central nervous system: mechanisms of cellular and molecular action].

The mechanisms of action of intravenous anaesthetics are not yet completely elucidated. Until recently, most of the studies had focused on the interactions between anaesthetics and lipid bilayers. It has been proposed that loss of consciousness is produced by disorganization of the lipid phase of nerve membranes, which impairs the action potential propagation. However, new data obtained with sophisticated neuropharmacological tools such as the patch clamp technique have recently contributed to challenge this hypothesis. Indeed, several lines of evidence suggest that intravenous anaesthetics are thought to induce loss of consciousness by blocking the excitatory synaptic transmission. This can be achieved presynaptically, by inhibiting glutamate release from nerve endings via alterations in the gating properties of voltage-dependent calcium channels. Blockade of excitatory synaptic transmission can also occur at the postsynaptic level by antagonizing the glutamate receptors of the N-methyl D-aspartate subtype. Some anaesthetic agents including ketamine also block the nicotinic receptors, however the relevance of this finding with respect to clinical anaesthesia requires further investigation. Preliminary data also suggest that propofol and etomidate elicit uncoupling of gap junctions between astrocytes, which represent a major nonneuronal cell population in the central nervous system. This phenomenon might indirectly contribute to the hypnotic action of these compounds. Whether loss of consciousness involves preferential target structures within the brain remains to be delineated. A better understanding of the mechanisms of action of general anaesthetics might contribute to generate new agents with more pharmacological selectivity and less undesirable side-effects.