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An upside-down binding mode to treat psychosis

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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.

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

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Acknowledgements

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

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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
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  2. Javier González-Maeso
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Correspondence to Javier González-Maeso.

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Competing interests

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

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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

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