Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

DRUG DESIGN

An upside-down binding mode to treat psychosis

Nature Neuroscience volume 25, pages 4–6 (2022)Cite this article

Subjects

The structural basis for the clinical and side effects of antipsychotic drugs has not been resolved. A new study combined X-ray crystallography with medicinal chemistry and behavioral pharmacology to design a new dopamine D2 receptor partial agonist that, in mice, shows not only antipsychotic-like activity but also 5-HT1A-receptor-dependent antidepressant-like effects.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: A new dopamine D2 receptor partial agonist to treat psychosis.

References

  1. Weis, W. I. & Kobilka, B. K. Annu. Rev. Biochem. 87, 897–919 (2018).

    Article  CAS  Google Scholar 

  2. Freedman, R. N. Engl. J. Med. 349, 1738–1749 (2003).

    Article  CAS  Google Scholar 

  3. Meltzer, H. Y. Annu. Rev. Med. 64, 393–406 (2013).

    Article  CAS  Google Scholar 

  4. Chen, Z. et al. Nat. Neurosci. https://doi.org/10.1038/s41593-021-00971-w (2021).

  5. Kimura, K. T. et al. Nat. Struct. Mol. Biol. 26, 121–128 (2019).

    Article  CAS  Google Scholar 

  6. Kim, K. et al. Cell 182, 1574–1588 (2020).

    Article  CAS  Google Scholar 

  7. Shah, U. H. et al. ACS Chem. Neurosci. 10, 2318–2331 (2019).

    Article  CAS  Google Scholar 

  8. Wang, S. et al. Nature 555, 269–273 (2018).

    Article  CAS  Google Scholar 

  9. Umbricht, D. et al. Arch. Gen. Psychiatry 57, 1139–1147 (2000).

    Article  CAS  Google Scholar 

  10. Moreno, J. L. & González-Maeso, J. Int. J. Neuropsychopharmacol. 16, 2131–2144 (2013).

    Article  CAS  Google Scholar 

  11. Davis, A. K. et al. JAMA Psychiatry 78, 481–489 (2020).

    Article  Google Scholar 

  12. Carhart-Harris, R. et al. N. Engl. J. Med. 384, 1402–1411 (2021).

    Article  CAS  Google Scholar 

  13. Glennon, R. A. NIDA Res. Monogr. 146, 4–32 (1994).

    CAS  PubMed  Google Scholar 

  14. Ly, C. et al. Cell Rep. 23, 3170–3182 (2018).

    Article  CAS  Google Scholar 

  15. Hesselgrave, N. et al. Proc. Natl Acad. Sci. USA 118, e2022489118 (2021).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by US National Institute of Mental Health grants R01MH084894 and R01MH111940 (J.G.-M.).

Author information

Authors and Affiliations

  1. Department of Physiology & Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA

    Alaina M. Jaster & Javier González-Maeso

  2. Department of Pharmacology & Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA

    Alaina M. Jaster

Authors
  1. Alaina M. Jaster
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Javier González-Maeso
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Javier González-Maeso.

Ethics declarations

Competing interests

J.G.-M. has a sponsored research contract with NeuRistic. A.M.J. declares no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jaster, A.M., González-Maeso, J. An upside-down binding mode to treat psychosis. Nat Neurosci 25, 4–6 (2022). https://doi.org/10.1038/s41593-021-00968-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41593-021-00968-5

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing