Interaction of psychotropic drugs with phospholipids

The interactions of psychotropic drugs with phospholipids, including lysophosphatidylcholine, phosphatidylinositol, and lysophosphatidylserine, were studied using calmodulin-dependent cyclic nucleotide phosphodiesterase partially purified from the cortex of hog brain. All the compounds used inhibited both calmodulin- and phospholipid-stimulated phosphodiesterase activity but not the basal activity. Fluphenazine was confirmed by kinetic analysis to be a competitive inhibitor, with both calmodulin and phospholipid. Using fluphenazine-Sepharose affinity chromatography, it was demonstrated that fluphenazine did not interact with the enzyme. The potencies of antipsychotics such as fluphenazine in inhibiting the various phospholipid-dependent activations decreased in the following order: lysophosphatidylcholine-, phosphatidylinositol-, and lysophosphatidylserine-dependent activation. On the other hand, antidepressant drugs exhibited similar inhibitory potencies towards lysophosphatidylcholine- and phosphatidylinositol-dependent activation. Antipsychotic and antidepressant drugs appear to have different characteristics with regard to lipid-drug interaction.