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Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia

Nature Reviews Drug Discovery volume 3, pages 353–359 (2004)Cite this article

Abstract

Most common central nervous system disorders — such as depression, bipolar disorder and schizophrenia — seem to be polygenic in origin, and the most effective medications have exceedingly complex pharmacologies. Attempts to develop more effective treatments for diseases such as schizophrenia and depression by discovering drugs selective for single molecular targets (that is, 'magic bullets') have, not surprisingly, been largely unsuccessful. Here we propose that designing selectively non-selective drugs (that is, 'magic shotguns') that interact with several molecular targets will lead to new and more effective medications for a variety of central nervous system disorders.

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Figure 1: Neuronal circuits implicated in schizophrenia aetiology and treatment.
Figure 2: Screening the receptorome reveals multiple molecular targets implicated in antipsychotic drug actions.

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Acknowledgements

Work in the authors' laboratories is supported by the National Institutes of Health.

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Authors and Affiliations

  1. Department of Biochemistry, School of Medicine, Case Western Reserve University, 2109 Adelbert Road, Cleveland, 44106, Ohio, USA

    Bryan L. Roth, Douglas J. Sheffler & Wesley K. Kroeze

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  1. Bryan L. Roth
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Correspondence to Bryan L. Roth.

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Competing interests

B.L.R. is a consultant for Arena Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly, Pfizer, Otsuka Pharmaceuticals, SK Corp. and Neotherapeutics. B.L.R. holds US patents on 5-HT-selective drugs.

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Roth, B., Sheffler, D. & Kroeze, W. Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia. Nat Rev Drug Discov 3, 353–359 (2004). https://doi.org/10.1038/nrd1346

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