Structural Features for Functional Selectivity at Serotonin Receptors

Abstract

Dissecting Serotonin Receptors Serotonin receptors are the targets for many widely used drugs prescribed to treat ailments from depression to obesity and migraine headaches (see the Perspective by Palczewski and Kiser ). C. Wang et al. (p. 610 , published online 21 March) and Wacker et al. (p. 615 , published online 21 March) describe crystal structures of two members of the serotonin family of receptors bound to antimigraine medications or to a precursor of the hallucinogenic drug LSD. Subtle differences in the way particular ligands bind to the receptors cause substantial differences in the signals generated by the receptor and the consequent biological responses. The structures reveal how the same ligand can activate one or both of the two main serotonin receptor signaling mechanisms, depending on which particular receptor it binds.

In the evidence

This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.

• State of the evidence: LSD ↑Supports

  Crystal structures of serotonin receptors bound to antimigraine drugs or an LSD precursor show that subtle ligand binding differences cause substantial differences in receptor signaling.

  Synthesized October 19, 2026

• State of the evidence: Serotonin ↑Supports

  Crystal structures of two serotonin receptor subtypes show that subtle ligand-binding differences cause substantial differences in receptor signaling and biological responses.

  Synthesized October 19, 2026