Spiradoline

Spiradoline (U-62066), an arylacetamide, is a selective kappa opioid receptor (KOR) agonist with a K_i of 8.6 nM in guinea pig. The K_i values of Spiradoline for μ and δ receptors are 252 nM and 9400 nM, respectively. Spiradoline has potent diuretic, analgesic, antiarrythmic, antitussive, neuroprotective properties and easily penetrates the blood-brain barrier^[1][2]. IC50 & Target: Ki: 8.6 nM (κ-opioid receptor in guinea pig), 252 nM (μ-receptor) and 9400 nM (δ-receptor)^[2] In Vitro: Using the patch-clamp method in isolated rat cardiac myocytes, indicated that Spiradoline (15 to 500 μM) produces its antiarrythmic effect via blockade of sodium channels (and at the higher doses also of potassium currents) in myocardial tissue. Thus, Spiradoline reduces the peak sodium current, increased the decay rate of the transient outward potassium current, and reduced the sustained plateau potassium amplitude^[2]. In Vivo: Spiradoline (U-62066; 0.1-0.4 mg/kg; subcutaneous injection; once; Sprague-Dawley rats) treatment dose-dependently reduces social behaviors in non-stressed adults, producing social avoidance at the highest dose tested, while younger animals displays reduced sensitivity to this socially suppressing effect of Spiradoline. In stressed animals, the socially suppressing effects of the Spiradoline are blunted at all ages, with juveniles and adolescents exhibiting increased social preference in response to certain doses of U-62066^[1].