Solubility, adsorption, and the thermodynamics of the cutoff effect

For many years, the expression “cutoff effect of anesthesia,” has been used to denote the failure of the higher alcohols or paraffins to produce anesthesia. As such, it is used to assess the plausibility of specific models, proposed for anesthesia. However, the uses were shown, in many respects, to be problematic. This article augments the notion of the cutoff to fit for all cases in which only some of the molecules in a homologous series are anesthetics. We find that the location of the cutoff points is affected by three free energy quantities: that of the adsorption of the agent to the anesthetic “site” (fsl,site), that of the perturbation of the site (fll,site), and that of the evaporation of the agent from its pure condensed phase (Δμoevaporation). This outcome indicates that the cutoff cannot be attributed to a single parameter. In addition, the analyses that attribute the cutoff to the failure of compounds to obey the much-used Meyer–Overton correlation will have to be amended. This article shows that cutoff results can be used to elucidate the structure of a site.