The thermodynamics of general anesthesia

It is known that the action of general anesthetics is proportional to their partition coefficient in lipid membranes (Meyer-Overton rule). This solubility is, however, directly related to the depression of the temperature of the melting transition found close to body temperature in biomembranes. We propose a thermodynamic extension of the Meyer-Overton rule, which is based on free energy changes in the system and thus automatically incorporates the effects of melting point depression. This model accounts for the pressure reversal of anesthesia in a quantitative manner. Further, it explains why inflammation and the addition of divalent cations reduce the effectiveness of anesthesia.