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A Molecular Model for Lithium's Bioactive Form.


ABSTRACT: Lithium carbonate, a drug for the treatment of bipolar disorder, provides mood stability to mitigate recurrent episodes of mania and/or depression. Despite its long-term and widespread use, the mechanism by which lithium acts to elicit these psychological changes has remained unknown. Using nuclear magnetic resonance (NMR) methods, in this study we characterized the association of lithium with adenosine triphosphate (ATP) and identified a bimetallic (Mg·Li) ATP complex. Lithium's affinity to form this complex was found to be relatively high (Kd ?1.6 mM) compared with other monovalent cations and relevant, considering lithium dosing and physiological concentrations of Mg(2+) and ATP. The ATP·Mg·Li complex reveals, for the first time, to the best of our knowledge, that lithium can associate with magnesium-bound phosphate sites and then act to modulate purine receptor activity in neuronal cells, suggesting a molecular mode for in vivo lithium action.

SUBMITTER: Briggs KT 

PROVIDER: S-EPMC4968421 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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A Molecular Model for Lithium's Bioactive Form.

Briggs Katharine T KT   Giulian Gary G GG   Li Gong G   Kao Joseph P Y JPY   Marino John P JP  

Biophysical journal 20160701 2


Lithium carbonate, a drug for the treatment of bipolar disorder, provides mood stability to mitigate recurrent episodes of mania and/or depression. Despite its long-term and widespread use, the mechanism by which lithium acts to elicit these psychological changes has remained unknown. Using nuclear magnetic resonance (NMR) methods, in this study we characterized the association of lithium with adenosine triphosphate (ATP) and identified a bimetallic (Mg·Li) ATP complex. Lithium's affinity to for  ...[more]

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