Drug-induced phase change in bilayer as possible mode of action of membrane expanding drugs

Abstract

MANY small molecules modulate membrane functions. Substances such as neurotransmitters interact directly with specific protein receptor sites, whereas others such as anaesthetics, interact with membrane lipids or with hydrophobic regions of membrane. This is consistent with a correlation of their activity with their lipid solubility and lipid–water partition coefficient¹. Several lipid-soluble drugs are antihaemolytic², which correlates not only with their pharmacological activity but also with their ability to expand the lipid bilayer of a biomembrane³. Although expansion of bilayers implies a drug-induced reorganisation of lipids, the mechanism involved remains to be established. We now have evidence that the lipid-soluble drugs may induce a transition of lipid acyl chains from organised gel to randomised liquid crystalline phase. Such drug-induced changes in the lipid phase in a bilayer may affect the function of various membrane-bound proteins⁴.