The pharmacology of simple molecules.

Abstract

The biological effects of simple molecules have traditionally been ascribed to their actions on the lipid portions of biological membranes. However, at the low concentrations of these molecules which induce general anaesthesia or have acute toxic effects in animals, changes in lipid bilayer properties are so small that they are unlikely to be relevant biologically. On the other hand, these molecules do inhibit the activity of a pure lipid-free protein, with ED50 concentrations which are essentially identical to the biological ED50 and LD50 concentrations. Moreover, the well-known but puzzling cutoffs in potencies in homologous series of compounds are also found with this enzyme. The accumulating evidence now suggests that the pharmacological effects of low concentrations of relatively inert agents are best explained in terms of their direct binding to amphiphilic pockets of circumscribed dimensions on proteins.