A structure-activity relationship study of psilocybin and psilocin derivatives found that 1-methylpsilocin acts as a selective agonist at the human 5-HT(2C) receptor. Its phosphate derivative, 1-methylpsilocybin, and 4-fluoro-N,N-dimethyltryptamine each showed efficacy in an animal model of obsessive-compulsive disorder. These findings point to a new avenue for developing novel 5-HT(2C) receptor agonists with potential applications in drug discovery.
Salvinorin A, a plant metabolite, is a potent and selective agonist of the human kappa-opioid receptor, which is being investigated as a target for new painkillers. This review examines analogs of the salvinorin chemotype and how modifications affect their selectivity, affinity, and potency. Extensive modifications to the periphery of the molecule, using isolated salvinorin A, have provided a wealth of structure-activity relationship (SAR) data. Recent advances in chemical synthesis now enable more fundamental changes to the core structure.