M3 General anesthesia (multi-target mechanisms)

Title

General anesthesia induces loss of consciousness and response to nociceptive stimuli through multiple simultaneous molecular mechanisms, mainly the potentiation of GABA-A inhibitory conductance (direct extension of the synaptic conductance of E04) and, in the case of dissociative agents such as ketamine, the blockade of NMDA receptors (extension of the receptor-ligand kinetics of E10, in the same line as the NMDA hypofunction of A07). Both mechanisms reduce effective cortical connectivity (W extension of E08) until the level of consciousness (defined in M01) falls below an operational threshold. The relationship between drug concentration and probability of loss of consciousness follows a Hill-type dose-response curve, while the pharmacokinetics of the agent is modeled with a simple compartmental scheme; The context-sensitive half-life reflects how the duration of the infusion prolongs the recovery time after discontinuing the drug.

ID:4275