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.
Two novel analogues of salvinorin A, EOM Sal B and β-THP Sal B, were tested in rats for their ability to reduce cocaine-related behaviors and their side effects. EOM Sal B dose-dependently reduced drug-seeking behavior in a reinstatement model and, along with β-THP Sal B, attenuated cocaine-induced hyperactivity without affecting general locomotion. Neither compound produced anxiety-like or depressive-like effects in the elevated plus maze or forced swim tests. However, β-THP Sal B caused aversion in the conditioned place aversion test. EOM Sal B showed no effect on sucrose self-administration, indicating selectivity for cocaine-related behaviors. EOM Sal B was more potent than salvinorin A and β-THP Sal B with fewer side effects.