Lusaperidone

Lusaperidone (R107474) is an α2 adrenergic receptor antagonist with K_is of 0.13 and 0.15 nM for α2A and α2C, respectively. IC50 & Target: Ki: 0.13 nM (α2A adrenergic receptor), 0.15 nM (α2C adrenergic receptor)^[1] In Vitro: Lusaperidone has subnanomolar affinity for α2A and α2C adrenergic receptor (K_i=0.13 and 0.15 nM, respectively) and shows nanomolar affinity for the hα2B adrenergic receptor and h5-HT7 receptors (K_i=1 and 5 nM, respectively). Lusaperidone interacts weakly (K_i values ranging between 81 and 920 nM) with dopamine-hD2L, -hD3 and -hD4, h5-HT1D-, h5-HT1F-, h5-HT2A-, h5-HT2C-, and h5-HT5A receptors. Lusaperidone, tested up to 10 μM, interacts only at micromolar concentrations or not at all with any of the other receptor or transporter binding sites tested in this study. Lusaperidone has been shown to reverse the clonidine-induced inhibition of cyclic AMP production mediated by human α2A and α2C adrenoceptors expressed in cell lines (K_b is 2.8 and 4.4 nM, respectively) and is a full antagonist on both receptor subtypes^[1]. In Vivo: Lusaperidone occupies the α2A and α2C adrenergic receptor with an ED₅₀ of 0.014 mg/kg sc (0.009-0.019) and 0.026 mg/kg sc (0.022-0.030), respectively. The uptake of R107474 after in vivo intravenous administration is very rapid; in most tissues (including the brain) it reaches maximum concentration at 5 min after tracer injection^[1].