Lithium - Effects
In animals, lithium administration does not induce behaviour disturbances, only at very high doses it can cause sedation.
In healthy subjects, lithium intake does not modify behaviour.
In patients with an acute state of manic-depressive disorder, (disease characterized by an alternation of episodes of depression and episodes of excitement called mania - bipolar form - ) the curative action of lithium, as well on the manic phase as on the depressive phase, exists but is less effective than that of neuroleptics or of usual antidepressants. But, in regular intakes, at a sufficient dosage to reach a plasma concentration between 0.5 and 0.8 mmol/ L, it has a recognized preventive action and induces a reduction or a suppression of the manic and depressive episodes.
Lithium has also a favorable effect in the treatment of atypical depressions, especially when they are cyclic or do not respond to usual antidepressants. In this case, lithium is often prescribed with antidepressants to reinforce their effect.
Several studies showed that lithium reinforced the antitumor effect of the TNF (Tumor necrosis factor) and the effect of interleukin 1. It increases secretion GM/CSF (Granulocyte - macrophage colony - stimulating Factor) which explains the hyperleucocytosis observed in the majority of patients treated by lithium. These observations show the possibility for new therapeutic uses of lithium.
Despite the indisputable efficacy of lithium in bipolar disorders, the studies performed in men and in animals, to find its mechanism of action have been disappointing. Research involving the modifications of the metabolism of biogenic amines did not give conclusive results. A modification of the activity of G proteins and modifications of the activity of calcium ATPase were suggested. Another possible explanation could be inhibition by lithium of enzymes implicated in the metabolism of inositides, in particular inositol-monophosphatase, responsible of the hydrolysis of inositolphosphates into inositol necessary for the regeneration of phospho-inositols. If the activity of lithium is based on the inhibition of inositolmonophosphatase, the inhibitors of this enzyme should also be effective, which would open the prospect for new drugs, perhaps more effective and better tolerated than lithium.
Inhibition of inositol monophosphate
Studies suggest that lithium has a neuroprotective effect by increasing the biosynthesis of bcl2 protein which inhibits apoptosis and by inhibiting an enzyme, the glycogen synthase kinase-3, which modulates the activity of several transcriptional factors.
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