Full text is available at the source.
Abstract
Agonist potencies at the 5-HT2A receptor were shown to increase with analogs having substituents at C-4 of the phenyl ring containing at least four heavy atoms.
- The serotonin 2A receptor is the most prevalent excitatory serotonin receptor in the brain.
- A hydrophobic tunnel adjacent to the orthosteric site was identified in experimental structures of the receptor.
- Molecular modeling and functional characterization were used to investigate the tunnel's role in receptor pharmacology.
- Substituents at C-4 of the phenyl ring in phenethylamine analogs can interact with the identified tunnel.
- These findings suggest that the tunnel may serve as a potential target for drug development.
Simplified