Salvinorin A (SalA) is a plant metabolite that agonizes the human kappa-opioid receptor (κ-OR) with high affinity and high selectivity over mu- and delta-opioid receptors. Its therapeutic potential has stimulated extensive semisynthetic studies and total synthesis campaigns. However, structural modification of SalA has been complicated by its instability, and efficient total synthesis has been...
Hallucinogens mediate many of their psychoactive effects by activating serotonin 2A receptors (5-HT 2A R). Although serotonin is the cognate endogenous neurotransmitter and is not considered hallucinogenic, metabolites of serotonin also have high affinity at 5-HT 2A R and can induce hallucinations in humans. Here we report that serotonin differs from the psychoactive N -methyltryptamines by its...
Serotonin and the hallucinogenic metabolites of tryptamines, dimethylated tryptamines, activate the serotonin 2A receptor (5‐HT2AR), which is implicated in numerous mental health disorders. We have previously demonstrated that the 5‐HT2AR is differentially regulated by βarrestin2 (βarr2) depending upon the agonist; here we utilized βarr2 knockout mice to compare signaling profiles in vivo, by...