Disease relevance of trifluoperazine

• Like bepridil, both TFP and W7 reduced the severity of arrhythmias evoked by 30 min of coronary artery occlusion in the anaesthetized rat [1].
• The presence of trifluoperazine (TFP; 50 microM), an antagonist of calmodulin, inhibited the effect of calcium (10 microM) addition in increasing NO synthase activity, indicating the existence of Ca(2+)/calmodulin-dependent NO synthase in hepatoma cells [2].
• Importantly, intensive apoptosis was also induced by TMX and TFP in the cells obtained from primary human breast carcinomas [3].
• Rapid and intensive induction of apoptosis was observed in estrogen receptor positive and negative breast cancer cell cultures treated with tamoxifen (TMX) combined with the calmodulin antagonists trifluoperazine (TFP) or W7 [3].

High impact information on trifluoperazine

• The potential antiarrhythmic and electrophysiological actions of drugs known to inhibit calmodulin, i.e. trifluoperazine (TFP) and N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide (W7) have been compared with bepridil, whose antiarrhythmic actions have previously been ascribed to blockade of the fast inward sodium current in cardiac tissue [1].
• The effect of regucalcin (10(-7) M) in decreasing NO synthase activity was also seen in the presence of TFP (50 microM) or EGTA (1 mM) [2].
• The biological implications from the cooperative, non-specific interaction of CPZ and TFP with membranes are also commented upon [4].
• Phenothiazine derivatives chlorpromazine (cpz) and trifluoperazine (tfp) were found to induce apoptosis, abnormal cell cycle and expression of p53 in Chinese hamster lung fibroblast V79 cells [5].
• Since it is known that the inhibitory effect of TFP or CHP against calmodulin-dependent enzymes such as phosphodiesterase is 100-400-fold higher compared to PMZ, it is speculated that the inhibitory effect of TFP or CHP against cyanide-induced convulsions may be based on its strong inhibitory properties into calmodulin-dependent enzymes [6].

Chemical compound and disease context of trifluoperazine

• Although TFP was shown to possess alpha-adrenoceptor blocking properties, the classical alpha-blocker, phentolamine, failed to reduce significantly the incidence or severity of reperfusion arrhythmias [1].

Biological context of trifluoperazine

• On the other hand, the LD50 value of cyanide was significantly increased by i.v.t. preadministration of TFP or CHP (0.045 mumol/body) [6].

Anatomical context of trifluoperazine

• These effects of calmodulin and TFP are consistent with the notion of a plasma membrane origin for this activity and also suggest that this activity could be a basis for the regulation of intracellular Ca2+ activity in the submicromolar range [7].
• The Ca2+ effect was significantly inhibited by trifluoperazine (TFP; 20 or 50 microM), an antagonist of calmodulin, indicating the existence of Ca2+/calmodulin-dependent NO synthase activity in rat heart muscle cytosol [8].
• Experiments using vesicles prepared from brush-border or basolateral membranes indicated that TFP inhibited the calcium-extrusion process, with virtually no effect on calcium entry [9].

Gene context of trifluoperazine

• Regucalcin significantly reduced NO synthase activity in the presence of TFP (50 micro micro M) or EGTA (1 mM) which has a significant inhibitory effect on the enzyme activity [10].

References