Possible Interaction: Arachidonic Acid and Trifluoperazine

“A 24-hr pretreatment of cultured human fibroblasts with trifluoperazine induced a marked increase in incorporation of saturated (stearic, palmitic) and unsaturated (oleic, arachidonic ) fatty acids into phospholipids (1.5- to 2-fold for 5.10−5 M trifluoperazine).”

“… TFP blocks effectively both … accumulation of free [3H]arachidonic acid and the mass of arachidonic acid without affecting the transfer of this fatty acid from PC to PE in thrombin-stimulated human platelets, it is very unlikely that the transacylation pathway represents a major source of release arachidonic acid.”

“We have found that aggregation by minimum concentrations of collagen and arachidonic acid , and second phase aggregation by minimum concentrations of ADP, thrombin, epinephrine and the calcium ionophore A23187 were inhibited by 40-60 microM trifluoperazine.”

“We have now demonstrated that trifluoperazine inhibits the production of all arachidonic acid metabolites, by both cyclooxygenase and lipoxygenase pathways, in thrombin-stimulated platelets.”

“EGTA, TFP and BAPTA/AM inhibited both arachidonic acid (AA) and PGE2 production without effecting COX-2 protein expression, but verapamil inhibited neither AA nor PGE2 production.”

“In addition, the A23187, but not the arachidonic acid stimulated Cl secretion was abolished in the presence of trifluoperazine , suggesting that the effect of the ionophore may be mediated via a Ca2+-calmodulin-dependent step located before the activation of the cyclooxygenase.”

“This epithelial action of arachidonic acid was inhibited by the calmodulin antagonist, trifluoperazine , and the intra-cellular Ca2(+)-antagonist, TMB-8.”

“The calmodulin inhibitor trifluoperazine (100 microM) inhibits stimulation of casein secretion by both prolactin and arachidonic acid.”

“… Trifluoperazine inhibits superoxide production and … pig neutrophils incubated with arachidonic acid , N-formylmethionylphenylalanine, digitonin or ionophore A23187, with IC 50 values of 7–37uM. Since this inhibition is produced by … interaction of calmodulin with proteins, we examined the effects of two other phenothiazines which interact less effectively with calmodulin.”