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A safe lithium mimetic for bipolar disorder

Author

Listed:
  • Nisha Singh

    (University of Oxford)

  • Amy C. Halliday

    (University of Oxford)

  • Justyn M. Thomas

    (University of Oxford)

  • Olga V. Kuznetsova

    (University of Oxford)

  • Rhiannon Baldwin

    (University of Oxford)

  • Esther C. Y. Woon

    (University of Oxford
    Present address: Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543)

  • Parvinder K. Aley

    (University of Oxford)

  • Ivi Antoniadou

    (University of Oxford)

  • Trevor Sharp

    (University of Oxford)

  • Sridhar R. Vasudevan

    (University of Oxford)

  • Grant C. Churchill

    (University of Oxford)

Abstract

Lithium is the most effective mood stabilizer for the treatment of bipolar disorder, but it is toxic at only twice the therapeutic dosage and has many undesirable side effects. It is likely that a small molecule could be found with lithium-like efficacy but without toxicity through target-based drug discovery; however, therapeutic target of lithium remains equivocal. Inositol monophosphatase is a possible target but no bioavailable inhibitors exist. Here we report that the antioxidant ebselen inhibits inositol monophosphatase and induces lithium-like effects on mouse behaviour, which are reversed with inositol, consistent with a mechanism involving inhibition of inositol recycling. Ebselen is part of the National Institutes of Health Clinical Collection, a chemical library of bioavailable drugs considered clinically safe but without proven use. Therefore, ebselen represents a lithium mimetic with the potential both to validate inositol monophosphatase inhibition as a treatment for bipolar disorder and to serve as a treatment itself.

Suggested Citation

  • Nisha Singh & Amy C. Halliday & Justyn M. Thomas & Olga V. Kuznetsova & Rhiannon Baldwin & Esther C. Y. Woon & Parvinder K. Aley & Ivi Antoniadou & Trevor Sharp & Sridhar R. Vasudevan & Grant C. Churc, 2013. "A safe lithium mimetic for bipolar disorder," Nature Communications, Nature, vol. 4(1), pages 1-7, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2320
    DOI: 10.1038/ncomms2320
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