Structural basis for partial agonism in 5-HT_3A receptors.

ABSTRACT: Hyperactivity of serotonin 3 receptors (5-HT₃R) underlies pathologies associated with irritable bowel syndrome and chemotherapy-induced nausea and vomiting. Setrons, a class of high-affinity competitive antagonists, are used in the treatment of these conditions. Although generally effective for chemotherapy-induced nausea and vomiting, the use of setrons for treating irritable bowel syndrome has been impaired by adverse side effects. Partial agonists are now being considered as an alternative strategy, with potentially less severe side effects than full antagonists. However, a structural understanding of how these ligands work is lacking. Here, we present high-resolution cryogenic electron microscopy structures of the mouse 5-HT_3AR in complex with partial agonists (SM

SUBMITTER: Felt K 

PROVIDER: S-EPMC12631364 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature