Evaluation of Biased and Balanced Salvinorin A Analogs in Preclinical Models of Pain
Frontiers in Neuroscience July 21, 2020 Kelly F. Paton, Andrew Biggerstaff, Sophia Kaska et al.
Two novel analogs of Salvinorin A, 16-Bromo SalA and 16-Ethynyl SalA, were tested for pain relief and side effects in mice. 16-Ethynyl SalA showed balanced signaling and produced strong, long-lasting antinociception in multiple pain models, including inflammatory pain, without causing anxiety. 16-Bromo SalA showed G-protein signaling bias, modest pain relief, and also lacked anxiogenic effects. Both analogs had longer duration of action than Salvinorin A and were more potent than the traditional KOPr agonist U50,488. These findings suggest that KOPr agonists can be designed to reduce aversive side effects while retaining analgesic properties.