S1RA (hydrochloride)

1265917-14-3

C20H24ClN3O2

DMSO : >= 57 mg/mL (152.46 mM)

GPCR/G Protein; Neuronal Signaling

S1RA hydrochloride (E-52862 hydrochloride) 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) [1] 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) [2]. 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 [2]. 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 [3].