A 31P NMR and Calorimetry Study: The Effects of an Antipsychotic Drug on Lipid Bilayers

Abstract

Hydrated dipalmitoylphosphatidylcholine (DPPC) multilayers were used as a model membrane system to study the effects of the antipsychotic drug chlorpromazine hydrochloride (CPZ) on the lipid phase transitions via ³¹P NMR spectroscopy and differential scanning calorimetry (DSC). ³¹P NMR results show a general increase in the chemical shift anisotropy values which can be attributed to interactions of the phospholipid with CPZ. DSC was used to measure the phase transition temperatures and enthalpy values at varying concentrations of CPZ in the multilayer. The DSC results show that CPZ lowers the phase transition temperature of DPPC and with increasing concentrations of CPZ in the bilayer, there is an additional peak which suggests the presence of a new phase, the interdigitated phase. Between 30 mol% and 50 mol% CPZ, there is a decrease in the chemical shift anisotropy values in the ³¹P NMR results which may be attributed to the interdigitated phase. Our studies also show CPZ begins to affect the lipid bilayers at concentrations lower than 2 mol% CPZ, as indicated by the presence of a small isotropic peak close to 0 ppm. This peak increases proportionally with increasing concentrations of CPZ. The lipid bilayer completely breaks up at 75 mol% CPZ, shown by the disappearance in the phosphorus multilamellar lineshape and an increase in the area of the isotropic peak.