[Centennial for the Meyer-Overton rule: anesthetics and receptors]

Abstract

As a backlash to the dominance of lipid theories of anesthesia for almost a century, protein theories are prevalent at present. Lipid theories assume nonspecific interaction with membranes. Protein theories assume specific interaction with specific receptors in specific proteins. The Meyer-Overton rule does not specify the anesthetic action site to lipid membranes. The correlation between the olive oil solubility to the anesthetic potency means that the action sites have similar physical properties to olive oil. It does not discriminate between lipids and proteins. Olive oil is homogeneous (isotropic) liquid whereas membranes and proteins are structured (anisotropic). The physical properties of proteins and membranes are not uniform throughout the structure. The rule shows that the anesthetics bind multiple areas in nonspecific proteins and membranes. The diversity of anesthetic structures is difficult to reconcile with the idea that there is a specific receptor on specific proteins.