Description
Trifluoperazine is a phenothiazine antipsychotic that is clinically used to treat schizophrenia and anxiety. Trifluoperazine also exhibits anxiolytic, anti-parasitic, anticancer, and anesthetic activities. This compound inhibits α1-adrenergic receptors, calmodulin, and D1/2 receptors. In Plasmodium, trifluoperazine inhibits Ca2+-dependent protein kinase 4 (CDPK4). In lung adenocarcinoma cells, trifluoperazine downregulates expression of F-actin and Bcl-2, upregulates expression of Bax and phosphorylation of ERK and JNK, induces apoptosis, and inhibits cellular proliferation. Additionally, this compound inhibits Nav1.4/SCNA4 and Nav1.7/SCN9A Na+ channels, causing sensory and motor blockade in vivo.
References
Cavagnino A, Rossi F, Rizzi M. The potent antiplasmodial calmodulin-antagonist trifluoperazine inhibits plasmodium falciparum calcium-dependent protein kinase 4. Protein Pept Lett. 2011 Dec;18(12):1273-9. PMID: 21787279.
Chen QY, Wu LJ, Wu YQ, et al. Molecular mechanism of trifluoperazine induces apoptosis in human A549 lung adenocarcinoma cell lines. Mol Med Rep. 2009 Sep-Oct;2(5):811-7. PMID: 21475906.
Sheets PL, Gerner P, Wang CF, et al. Inhibition of Nav1.7 and Nav1.4 sodium channels by trifluoperazine involves the local anesthetic receptor. J Neurophysiol. 2006 Oct;96(4):1848-59. PMID: 16807347.
Creese I, Burt DR, Snyder SH. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. J Neuropsychiatry Clin Neurosci. 1996 Spring;8(2):223-6. PMID: 9081563.
Huerta-Bahena J, Villalobos-Molina R, García-Sáinz JA. Trifluoperazine and chlorpromazine antagonize alpha 1- but not alpha2- adrenergic effects. Mol Pharmacol. 1983 Jan;23(1):67-70. PMID: 6135146.
Yano T, Kassovska-Bratinova S, Teh JS, et al. Reduction of clofazimine by mycobacterial type 2 NADH:quinone oxidoreductase: a pathway for the generation of bactericidal levels of reactive oxygen species. J Biol Chem. 2011 Mar 25;286(12):10276-10287. PMID: 21193400.