Lusaperidone (R107474) is a potent α2-adrenergic receptor antagonist, a potential radioligand for the α (2)-adrenergic receptor, with inhibitory effects on α2A and α2C, with Ki values of 0.13 and 0.15 nM, respectively.

H5-HT7 receptor:5 nM(Ki), α2A-adrenoceptor:0.13 nM (Ki), α2A-adrenoceptor:2.8 nM (Kb,human), α2B-adrenoceptor (human):1 nM (Ki), α2C-adrenoceptor:0.15 nM(Ki), α2C-adrenoceptor:4.4 nM (Kb,human)

Lusaperidone exhibits subnanomolar affinity for α2A and α2C adrenergic receptors (Ki=0.13 and 0.15 nM, respectively) and demonstrates nanomolar affinity for hα2B adrenergic receptors and h5-HT7 receptors (Ki=1 and 5 nM, respectively). It interacts weakly (Ki 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. Furthermore, Lusaperidone has been demonstrated to reverse the clonidine-induced inhibition of cyclic AMP production mediated by human α2A and α2C adrenoceptors expressed in cell lines (Kb is 2.8 and 4.4 nM, respectively) and acts as a full antagonist on both receptor subtypes[1].

Lusaperidone occupies the α2A and α2C adrenergic receptors 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 is very rapid after in vivo intravenous administration; in most tissues, including the brain, it reaches maximum concentration at 5 min after tracer injection[1].