The structural diversity of psychedelic drug actions revealed.

ABSTRACT: There is currently a resurgence in exploring the utility of classical psychedelics to treat depression, addiction, anxiety disorders, cluster headaches, and many other neuropsychiatric disorders. A biological target of these compounds, and a hypothesized target for their therapeutic actions, is the 5-HT_2A serotonin receptor. Here, we present 7 cryo-EM structures covering all major compound classes of psychedelic and non-psychedelic agonists, including a β-arrestin-biased compound RS130-180. Identifying the molecular interactions between various psychedelics and the 5-HT_2A receptor reveals both common and distinct motifs among the examined psychedelic chemotypes. These findings lead to a broader mechanistic understanding of 5-HT_2A activation, which can catal

SUBMITTER: Gumpper RH 

PROVIDER: S-EPMC11923220 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature