Exploring Novel Antidepressants Targeting G Protein-Coupled Receptors and Key Membrane Receptors Based on Molecular Structures.
Molecules (Basel, Switzerland) February 22, 2024 Hanbo Yao, Xiaodong Wang, Jiaxin Chi et al. 9 citations
Major Depressive Disorder involves changes in signal transmission and brain structure. Progress in developing effective antidepressants has been slow due to the dominance of the monoamine hypothesis, and traditional drugs often have delayed effects, limited efficacy, and severe side effects. Recently, fast-acting compounds like S-ketamine and psychedelics such as LSD have emerged, prompting structural research on their target receptors. Cryo-electron microscopy has enabled high-resolution structures of the N-methyl-D-aspartate receptor and the 5-hydroxytryptamine 2A receptor, which can be used for virtual drug screening. The 5-HT1A receptor shows unique antidepressant effects in different brain regions, while AMPAR and TrkB receptors regulate synaptic plasticity. Using this structural information, highly selective antidepressants with rapid onset and fewer side effects have been designed.