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Pathway-selective 5-HT1AR agonist speeds up antidepressant effect

By
  1. M. Teresa Villanueva

The serotonin 1A receptor (5-HT1AR), a key regulator of mood and a well-established antidepressant target, operates as both presynaptic autoreceptors and postsynaptic heteroreceptors in the brain. Achieving selective activation of heteroreceptors while avoiding autoreceptor-driven inhibitory feedback has been challenging. Now, writing in Cell, Wang et al. have characterized the signalling profiles of 5-HT1AR and designed a novel heteroreceptor-selective agonist, TMU4142, which demonstrates rapid antidepressant effects in mice.

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Nature Reviews Drug Discovery 25, 20 (2026)

doi: https://doi.org/10.1038/d41573-025-00201-z

References

  1. Wang, C. et al. Pathway-selective 5-HT1AR agonist as a rapid antidepressant strategy. Cell https://doi.org/10.1016/j.cell.2025.10.022 (2025)

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