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Drug discovery

Zebrafish uncover novel antipsychotics

Nature Chemical Biology volume 12, pages 468–469 (2016)Cite this article

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Two independent high-throughput zebrafish behavioral screens of tens of thousands of compounds identify the 'finazines', a novel group of antipsychotics, and their endogenous genetic target, the σ1 receptor.

The high demand for effective novel therapies against psychiatric disorders far outstrips supply, with new drug development seemingly stalling1. On the one hand, the problem may lie with both a basic lack of understanding of the highly complex biological mechanisms governing these disorders and an overreliance on in vitro cell or organotypic chemical assays that may not fully recapitulate this complexity. On the other hand, psychiatric drug screening in nonhuman models such as rodents are prohibitively costly, are not amenable to high-throughput screening of large chemical drug libraries (a conservative estimate is that 50,000 mice are required for a typical 10,000-drug screen), and have a low success rate through clinical trials. Thus, there is an urgent need for new alternatives for cheaper, rational, and more targeted generation of new drug leads.

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Figure 1: Vertebrate pipeline for drug screening, genetic target validation, and future clinical trials.

Katie Vicari / Nature Publishing Group

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Authors and Affiliations

  1. Department of Psychiatry & Behavioral Sciences, Louis C. Leung & Philippe Mourrain are in the Stanford Center for Sleep Sciences and Medicine, Stanford University, Stanford, California, USA.,

    Louis C Leung & Philippe Mourrain

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  1. Louis C Leung
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  2. Philippe Mourrain
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Correspondence to Philippe Mourrain.

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The authors declare no competing financial interests.

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Leung, L., Mourrain, P. Zebrafish uncover novel antipsychotics. Nat Chem Biol 12, 468–469 (2016). https://doi.org/10.1038/nchembio.2114

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