S1RA hydrochloride (E-52862 hydrochloride) is an effective and specific sigma-1 receptor(σ1R, Ki: 17 nM) antagonist, and has good selectivity against σ2R (Ki > 1000 nM).

σ1:17 nM

S1RA showed high affinity for the guinea pig (Ki: 23.5 nM) and human (Ki: 17 nM) σ1 receptors but no marked affinity for the σ2 receptors (Ki > 1000 nM for guinea pig and rat σ2 receptors). Moderate affinity (Ki: 328 nM) and antagonistic activity with very low potency (IC50: 4700 nM) were found at the human 5-HT2B receptor. S1RA showed a low affinity (Ki > 1 μM, IC50>1 μM) for other additional 170 targets (transporters, receptors, ion channels and enzymes).

Control (non-operated) and nerve-injured mice received a single or repeated (b.i.d, for 12 days) S1RA (25 mg/kg, i.p.), the same dose used for the assessment of behavioral hypersensitivity in the chronic treatment study. In the behavioral studies, acute treatment was given on day 12 post-surgery and repeated treatment with S1RA started the day of surgery. Intrathecal pre-treatment with idazoxan prevented the systemic S1RA antinociceptive effect, suggesting that the S1RA antinociception depends on the activation of spinal α2 -adrenoceptors which, in turn, could induce an inhibition of formalin-evoked glutamate release. When administered locally, intrathecal S1RA inhibited only the flinching behavior, whereas intracerebroventricularly or intraplantarly injected also attenuated the lifting/licking behavior.