Interaction of chlorpromazine and imipramine with model membranes

The aim of the present study is to examine the effect of phospholipids on the lipid destabilization induced by chlorpromazine (CPZ) and imipramine (IP) at different levels of pH. The large unilamellar vesicles (LUV) are formed in the presence of calcein (60 mM). The vesicles containing calcein have been incubated in the presence of CPZ and IP at pH 4.5 and pH 8. At pH 4.5 CPZ and IP induce a rapid release of the calcein encapsulated in the liposomes. Calcein release, at equal concentrations of pharmacological agent, is more important by CPZ than by IP. At pH 8, the calcein release was more important than at pH 4.5; this effect appears to be more significant for the CPZ than for the IP. In conclusion, the insertion of chlorpromazine and imipramine into large unilamellar vesicles is accompanied by a strong destabilization of the vesicles. These effects appear more significant for chlorpromazine than for imipramine.