1. Academic Validation
  2. A safe lithium mimetic for bipolar disorder

A safe lithium mimetic for bipolar disorder

  • Nat Commun. 2013;4:1332. doi: 10.1038/ncomms2320.
Nisha Singh 1 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 Churchill
Affiliations

Affiliation

  • 1 University of Oxford, Department of Pharmacology, Mansfield Road, Oxford OX1 3QT, UK.
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.

Figures
Products