Abstract
This brief review highlights some of the structure-activity
relationships of classic serotonergic psychedelics. In particular, we
discuss structural features of three chemotypes: phenethylamines,
ergolines, and certain tryptamines, which possess psychedelic activity
in humans. Where it is known, we point out the underlying molecular
mechanisms utilized by each of the three chemotypes of psychedelic
molecules. With a focus on the serotonin 5-HT2A receptor subtype, a
G-protein coupled receptor known to be the primary target of
psychedelics, we reference several x-ray and cryoEM structures with
various ligands bound to illustrate the underlying atomistic basis for
some of the known pharmacological observations of psychedelic drug
actions.