Mood disorders are relatively common serious human diseases for which there is often no ideal pharmacotherapy. Basic characteristic of these diseases is affective disorder shifting the mood of the patient to depression (together with anxiety or not) or towards to euphoria. Available drugs are usually divided into two groups - mood stabilizers, which are used primarily to treat bipolar disorder, and antidepressants for the treatment of unipolar depression. Lithium is still recommended as the first choice for dealing with bipolar disorder. Despite abundant clinical use of mood stabilizing drugs, important questions regarding their mechanism of action remain open. In this paper we present the brief review of rather diversified hypotheses and ideas about mechanisms of genesis of mood disorders and lithium interferences with these pathological states. New data derived from the high-resolution crystallographic studies of allosteric, Na+-binding sites present in G protein coupled receptors are given together with data indicating the similarity between lithium and magnesium cations. In this context, similarities and dissimilarities between the useful "poison" with narrow therapeutic window (Li+) and the bivalent cation acting like cofactor of more than 300 enzymatic reactions (Mg2+) are pointed out together with results indicating enhanced activity of trimeric G proteins in bipolar disorder.

Department of Biomathematics Institute of Physiology of the Czech Academy of Sciences Prague Czech Republic;

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Exemplar scoring identifies genetically separable phenotypes of lithium responsive bipolar disorder