Dimemorfan phosphate (3,17-dimethylmorphinan) is a sigma 1 receptor agonist. Dimemorfan phosphate is used as a potent antitussive.

σ1 receptor:150 nM(Ki)

Dimemorfan, at concentrations of 5-20 μM, concentration-dependently inhibits ROS production induced by fMLP and PMA, demonstrating greater potency against fMLP-induced ROS with an IC50 of 7.0 μM. At higher concentrations (10-50 μM), it does not significantly scavenge free radicals in the xanthine/xanthine oxidase system. Moreover, Dimemorfan effectively reduces Mac-1 upregulation and notably suppresses ROS and NO production induced by LPS in the 10-20 μM range. It also diminishes LPS-induced iNOS protein expression and decreases both the percentage and the median channel fluorescence (MCF) intensities of MCP-1 and TNF-α in the BV2 cytosol. At a concentration of 20 μM, Dimemorfan significantly inhibits the degradation of cytosolic Iκ-Bα, hinders the nuclear translocation of NF-κB p65, and curtails the transcriptional activity of NF-κB, showcasing its multifaceted inhibitory effects on inflammation-related mechanisms.

Dimemorfan, administered subcutaneously at doses of 6.25 or 12.5 mg/kg, significantly reduces BAY k-8644-induced convulsive behaviors in mice in a dose-dependent manner, as evidenced by a comparison of groups receiving dimemorfan and BAY k-8644 (6.25 mg/kg or 12.5 mg/kg) versus a control group treated with saline and BAY k-8644 (P<0.05 and P<0.01, respectively). Additionally, dimemorfan markedly decreases the BAY k-8644-stimulated elevation of c-fos and c-jun protein expression, also in a dose-related fashion. Notably, dimemorfan does not significantly impact mice's locomotor activity nor induce notable circling behavior. Moreover, intraperitoneal injections of dimemorfan (1 and 5 mg/kg) suppress the rise in plasma TNF-α levels in mice. Furthermore, dimemorfan treatment effectively hampers the infiltration of neutrophils into the lung and liver as well as decreases oxidative stress, evidenced by EB staining, in these organs following LPS challenge.