Trifluoperazine-d₃is intended for use as an internal standard for the quantification of trifluoperazine by GC- or LC-MS. Trifluoperazine (TFP) is a phenothiazine compound with anti-adrenergic and anti-dopaminergic actions typical of antipsychotic agents.¹It antagonizes adrenergic receptors, with selectivity for α₁over the α₂subtypes (K_is = 24, 653, 163, and 391 nM for α_1A, α_2A, α_2B, and α_2C, respectively). TFP binds with much higher affinity to the dopamine D₂-like receptor (K_d= 0.96 nM) compared to the dopamine D₄-like and the serotonin 5-HT_2Areceptors (K_ds = 44 and 135 nM, respectively).²Furthermore, TFP antagonizes calmodulin (CaM) and alters the calcium-binding properties of calsequestrin (CSQ).^3,4TFP has been shown to activate type-2 ryanodine receptors independently of its CaM and CSQ activity.⁴

1.Kroeze, W.K., Hufeisen, S.J., Popadak, B.A., et al.H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugsNeuropsychopharmacology28(3)519-526(2003) 2.Seeman, P., Corbett, R., and Van Tol, H.H.Atypical neuroleptics have low affinity for dopamine D2 receptors or are selective for D4 receptorsNeuropsychopharmacology16(2)93-110(1997) 3.Zimmer, M., and Hofmann, F.Calmodulin antagonists inhibit activity of myosin light-chain kinase independent of calmodulinEur. J. Biochem.142(2)393-397(1984) 4.Qin, J., Zima, A.V., Porta, M., et al.Trifluoperazine: A ryanodine receptor agonistPflugers Arch.458(4)643-651(2009)