Trifluoperazine-d3 is 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.1 It antagonizes adrenergic receptors, with selectivity for α1 over the α2 subtypes (Kis = 24, 653, 163, and 391 nM for α1A, α2A, α2B, and α2C, respectively). TFP binds with much higher affinity to the dopamine D2-like receptor (Kd = 0.96 nM) compared to the dopamine D4-like and the serotonin 5-HT2A receptors (Kds = 44 and 135 nM, respectively).2 Furthermore, TFP antagonizes calmodulin (CaM) and alters the calcium-binding properties of calsequestrin (CSQ).3,4 TFP 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)