Chemistry/structural biology of psychedelic drugs and their receptor(s).
British journal of pharmacology – October 02, 2024
Source: PubMed
Summary
Recent breakthroughs in understanding how psychedelic compounds like LSD and psilocybin interact with brain receptors are revolutionizing therapeutic approaches. Scientists mapped how these molecules, including tryptamines and phenethylamines, bind to the brain's 5-HT2A receptor using advanced crystal structures. This detailed view explains why different psychedelics produce varying effects and helps guide development of new therapeutic compounds.
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 they are known, we point out the underlying molecular mechanisms utilized by each of the three chemotypes of psychedelic molecules. With a focus on the 5-HT2A receptor subtype, a G-protein coupled receptor known to be the primary target of psychedelics, we refer to several X-ray and cryoEM structures, with a variety of ligands bound, to illustrate the underlying atomistic basis for some of the known pharmacological observations of psychedelic drug actions.