The sigma-1 (σ1) receptor is an intracellular, non-opioid receptor that is abundantly expressed in the central nervous system as well as peripherally. S1RA is a potent, selective antagonist of σ1 receptors (Ki = 17 nM) that weakly binds σ2 receptors (Ki = 9,300 nM). It is active in vivo, dose-dependently inhibiting neuropathic pain in several animal models, including formalin-induced nociception and capsaicin-induced mechanical hypersensitivity. S1RA enhances peripheral μ-opioid analgesia without affecting opioid-induced constipation.
