Salvinorin A, a potent and selective kappa opioid receptor agonist, produces intense hallucinogenic effects when smoked. The smoke of salvinorin A contains at least eight neoclerodane diterpene derivatives, which were isolated and identified using spectroscopic methods. The major chemical transformations occurring during smoking include epimerizations, eliminations, and rearrangements, leading to these novel compounds.
Salvinorin A, the main active ingredient of Salvia divinorum, is a potent and selective kappa-opioid receptor agonist. A series of C-12 triazole analogs and an oxadiazole analog were synthesized and tested for binding affinity at kappa, mu, and delta opioid receptors. Surprisingly, all triazole analogs showed negligible binding affinity at opioid receptors, and the oxadiazole analog, previously reported as a mu and kappa opioid receptor antagonist, exhibited very low affinities and no antagonism in the binding assays. These results suggest that electronic factors affecting either the electron density of a hydrogen bond acceptor at C-12 or hydrophobic interactions between the C-12 moiety and the kappa-opioid receptor are critical for C-12 analog affinity.