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Review
. 2024 Oct 2.
doi: 10.1111/bph.17361. Online ahead of print.

Chemistry/structural biology of psychedelic drugs and their receptor(s)

Ryan H Gumpper  1 , David E Nichols  1
Affiliations
Free article
Review

Chemistry/structural biology of psychedelic drugs and their receptor(s)

Ryan H Gumpper et al. Br J Pharmacol. .
Free article

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.

Keywords: 5‐HT2A agonists; 5‐HT2A receptor; LSD; Psychedelic chemotypes; crystal structures; docking; ergolines; phenethylamines; psilocybin; structural biology; structure‐activity relationships; therapeutic potential; tryptamines.

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