S1RA hydrochloride

Sigma receptor

-20

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).

S1RA Hcl(E-52862 Hcl) is a potent and selective sigma-1 receptor(sigma1R, Ki=17 nM) antagonist, showed good selectivity against sigma2R (Ki > 1000 nM). IC50 value: 17 nM (Ki) Target: sigma1R antagonist in vitro: S1RA behaved as a highly selective sigma1 receptor antagonist. It showed high affinity for human (Ki= 17 nM) and guinea pig (Ki= 23.5 nM) sigma1 receptors but no significant affinity for the sigma2 receptors (Ki > 1000 nM for guinea pig and rat sigma2 receptors). Moderate affinity (Ki= 328 nM) and antagonistic activity, with very low potency (IC50= 4700 nM) was found at the human 5-HT2B receptor. S1RA showed no significant affinity (Ki > 1 uM or % inhibition at 1 uM < 50%) for other additional 170 targets (receptors, transporters, ion channels and enzymes) . in vivo: Control (non-operated) and nerve-injured mice received a single or repeated (twice daily for 12 days) i.p. administration of S1RA at 25 mg·kg?1, the same dose used for the assessment of behavioural hypersensitivity in the chronic treatment study. Acute treatment was given on day 12 post-surgery and repeated treatment with S1RA started the day of surgery, as in the behavioural studies . Intrathecal pre-treatment with idazoxan prevented the systemic S1RA antinociceptive effect, suggesting that the S1RA antinociception depends on the activation of spinal alpha2 -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 .