S1RA (E-52862) is a highly selective σ1 receptor (σ1R) antagonist with Kis of 17 nM and 23.5 nM for human σ1R and guinea pig σ1R, respectively. Its activity extends moderately towards the human 5-HT2B receptor with a Ki of 328 nM. This selectivity profile is complemented by its antinociceptive capabilities in models of neuropathic pain, demonstrating efficacy in preventing both mechanical and cold hypersensitivity in mice treated with Oxaliplatin[1][2].
体内研究
In vivo, a single intraperitoneal (IP) dose of S1RA at 40 mg/kg leads to a significant reduction in pain responses induced by Allylisothiocyanate (AITC) in wild-type (WT) mice. Further demonstrating its analgesic potential, the same dosing regimen, administered once daily for 11 days starting 3 days before Oxaliplatin injection, effectively counters mechanical and cold hypersensitivity induced by the chemotherapy agent Oxaliplatin in mice[2].
体外研究
In cell-based assays, S1RA at a concentration of 100 µM over 4 hours can inhibit intracellular calcium responses in TRPA1-expressing HEK293 cells, illustrating its potential for modulating ion channel activities. It also impairs the formation of TRPA1–Sigma-1R complexes and reduces TRPA1 expression at the plasma membrane, which could underlie some of its therapeutic effects[2].
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