A potent and selective kappa opioid receptor (KOPr) analogue of Salvinorin A, Mesyl Sal B, reduces cocaine-induced hyperactivity and behavioral sensitization to cocaine in male rats without causing aversion, sedation, anxiety, or learning and memory deficits. It does not alter sucrose self-administration. However, it increases immobility in the forced swim test, indicating pro-depressive effects. In male mice, Mesyl Sal B is less potent than Salvinorin A at reducing pain in antinociceptive assays. The compound has fewer side effects and longer in vivo action than Salvinorin A, but its pain-relieving effects are limited.
Kappa opioid receptor (KOR) agonists, including analogues of Salvinorin A, reduced pain in a mouse model of chemotherapy-induced neuropathic pain. 16-Ethynyl SalA was more potent than morphine at reducing mechanical allodynia, and SalA, 16-Ethynyl SalA, and EOM SalB were more potent at reducing cold allodynia. Sex differences appeared in mechanical allodynia testing: U50,488 was more potent in males, SalA more potent in females, but no sex differences occurred in cold allodynia. Chronic U50,488 (10 mg/kg) restored mechanical and cold pain responses to healthy levels over 23 days. KOR agonists may be developed to treat this condition.