Chemistry/structural biology of psychedelic drugs and their receptor(s).
Ryan H. Gumpper, David E Nichols
British Journal of Pharmacology October 2, 2024 DOI: 10.1111/bph.17361 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | LSD Psilocybin |
| Keywords | Psychedelic research Drug development Molecular biology Receptor binding 5‐ht2a agonists 5‐ht2a receptor Psychedelic chemotypes Crystal structures Docking Ergolines Phenethylamines Structural biology Structure‐activity relationships Therapeutic potential Tryptamines |
| Citations | 9 |
| Key findings | Three chemotypes of classic serotonergic psychedelics—phenethylamines, ergolines, and tryptamines—have distinct structural features that determine their activity at the 5-HT2A receptor, and recent structural biology studies reveal the atomic basis for their pharmacological effects. |
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.