Publication

Abstract : This work presents the non-specific action of midazolam (MDZ) on planar bilayer lipid membranes (BLMs), studied by following the dose-dependent changes in the electrical characteristics of BLMs. MDZ is found to interact with the polar regions or the hydrocarbon core of the membrane depending on whether it exists in charged or neutral form. The extent of these interactions depends on the ionic strength of the medium supporting the membrane, which influences the proportions of the charged and neutral forms of MDZ present in the medium. The observed electrical characteristics of the membranes are a consequence of competitive effects brought about by these drug species on both regions of the membrane. The drug is observed to impart a stabilizing effect at low doses and a destabilization above a saturation level at the polar regions of the lipids. These results demonstrate that the level of MDZ necessary for the destabilization and fluidization effect on biomembranes is close to that obtained after a single dose, and that its continuous administration in the spinal cord is neurotoxic. © 2014 Elsevier Ltd.