S1RA hydrochloride, the orally active form of S1RA, retains high selectivity for the σ1R over σ2R, with Ki values significantly greater than 1000 nM for the latter. Despite its moderate antagonism of the human 5-HT2B receptor (with an IC50 of 4.7 μM), S1RA hydrochloride's primary pharmacological effect is mitigating neuropathic pain and preventing activity-induced spinal sensitization[1][2].
体内研究
S1RA hydrochloride has shown efficacy in various pain models, significantly inhibiting formalin-induced nociception, capsaicin-induced mechanical hypersensitivity, and sciatic nerve injury-induced mechanical and thermal hypersensitivity in mice, across a wide dose range through both intraperitoneal and oral administration[1].
体外研究
S1RA hydrochloride distinguishes itself as a highly selective antagonist for the sigma-1 receptor (σ1R), with strong affinity indicated by Ki values of 17 nM and 23.5 nM for human and guinea pig σ1Rs, respectively. Its affinity extends to the human σ2R, albeit at a much higher Ki value of 9.3 μM, demonstrating its selectivity towards σ1R. Additionally, S1RA hydrochloride targets the human 5-HT2B receptor, with a Ki value of 328 nM and an IC50 value of 4.7 μM, indicating a moderate antagonistic activity[1].
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