Trifluoperazine (TFP) is a phenothiazine compound with anti-
adrenergic and anti-
dopaminergic actions typical of antipsychotic agents. It antagonizes adrenergic receptors, with selectivity for α
1 over the α
2 subtypes (K
is = 24, 653, 163, and 391 nM for α
1A, α
2A, α
2B, and α
2C, respectively).
1 TFP binds with much higher affinity to the dopamine D
2-
like receptor (K
d = 0.96 nM) compared to the dopamine D
4-
like and the serotonin 5-
HT
2A receptors (K
ds = 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