Does the Meyer-Overton Correlation Need to be Modified

Abstract

The linear relationship between the partition coefficient and anaesthetic potency is known as Meyer-Overton correlation. The homologous series of n-alcanols, upon elongation, shows increasing anaesthetic potency accompanied by an increase of the partition coefficient. However, the anaesthetic potency drops at a certain chain length although the partition coefficient still increases. This is known as cut-off effect. Although the cut-off effect is seemingly contradicting the Meyer-Overton correlation, we would like to show that the universal validity of the Meyer-Overton correlation still applies.Instead of anaesthetic potency, the cut-off effect can also be described by the melting transition temperature of lipids. Recently, we have provided a thermodynamic theory to describe the principle of the freezing point depression, i.e. the anaesthetic solves better in the fluid phase of the membrane than the gel phase. Similarly, it has been shown that the longer n-alcanols cause an increase in the transition temperature. This indicates that these non-anaesthetic n-alcanols solve better in the gel phase of the membrane than the fluid phase, and we, therefore, suggest to extend the Meyer-Overton correlation to differentiate between solubility in the membrane and solubility in the fluid phase of the membrane.