2009 issue 1


Volume 25, issue 1

Only for Pharmacotherapy in Psychiatry and Neurology

Biological mechanisms of lithium action in the context of mood-stabilizing effect

Agnieszka Permoda-Osip1, Janusz Rybakowski1
1. Klinika Psychiatrii Dorosłych Uniwersytetu Medycznego w Poznaniu
Farmakoterapia w Psychiatrii i Neurologii, 2009, 1, 7–15
Keywords: lithium, bipolar affective illness, neurotransmission, phosphatidylinositol system, neuroprotection, immunomodulation


In this paper, the attempt was made of summing up the knowledge on the mechanisms of action of lithium – the oldest normothymic drug used for the treatment and prophylaxis of bipolar affective illness. Current neurobiological and molecular genetic studies enable better understanding of the mechanism of prophylactic effect of lithium in bipolar patients. Lithium infl uences cell membrane transport, among others by stimulating the activity of sodium-potassium adenosinotriphosphate (ATPase) and by stabilizing intracellular sodium level. As to its effect on neurotransmission, lithium exerts a signifi cant effect on serotoninergic system (an increase of serotonin synthesis, 5HT2A receptor inhibition, selective modifi cation of 5HT2A/2C and 5HT1B receptors), on dopaminergic transmission (blocking dopaminergic receptor hypersensitivity, conformational alterations of dopamine D2 receptors), on noradrenergic transmission (increasing noradrenaline inactivation and reducing an availability of this neurotransmitter on synapses), and on glutaminergic and GABA-ergic transmission (lithium-induced reduction of glutaminic acid in basal ganglia, and an increase of GABA levels in prefrontal cortex). Especially important role has been assumed for lithium effect on second messenger systems, particularly on phosphatidylinositol and cyclic adenosinomonophosphate (cAMP). This effect may be intimately linked to pathogenic mechanisms of bipolar illness as well as to mechanisms of other fi rst generation mood stabilizing drugs (carbamazepine, valproates). In the paper, the processes connected with neuroprotective action of lithium such as activation of the brain derived neurotrophic factor (BDNF), an increase of bcl-2 protein concentration and inhibition of glycogen synthase kinase (GSK-3) have been also described. The evidence has been presented for the role of some processes in the mechanism of lithium prophylactic effect, obtained on the basis of own molecular-genetic studies in patients with different prophylactic effect of lithium. In the fi nal chapter, some aspect of immunomodulatory and anti-viral effects of lithium have been discussed which may be of signifi cance for normothymic effect of this ion in bipolar illness.

Address for correspondence:
Klinika Psychiatrii Dorosłych Uniwersytetu Medycznego
ul. Szpitalna 27/33, 60-572 Poznań
tel. 061 8475087, fax. 061 8480392,
E-mail autora korespondującego: a.a.p@wp.pl