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.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002846:Chromatography, Affinity; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D005476:Fluphenazine / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008244:Lysophosphatidylcholines / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011619:Psychotropic Drugs / Q000494:pharmacology*; D013552:Swine
D002147:Calmodulin; D008244:Lysophosphatidylcholines; D010716:Phosphatidylinositols; D010743:Phospholipids; D011619:Psychotropic Drugs; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D005476:Fluphenazine