Current Medicinal Chemistry
1875-533X/20 $65.00+.00 © 2020 Bentham Science Publishers
Branislava Medić
1,*
, Marko Stojanović
1
, Bojan V. Stimec
2
, Nevena Divac
1
,
Katarina Savić Vujović
1
, Radan Stojanović
1
, Mirjana Čolović
3
, Danijela Krstić
4
and
Milica Prostran
1
1
Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of
Belgrade, Belgrade, Serbia;
2
Anatomy Sector, Department of Cell Physiology and Metabolism, Faculty of
Medicine, University of Geneva, Geneva, Switzerland;
3
Department of Physical Chemistry, “Vinča“ Institute
of Nuclear Sciences, University of Belgrade, Belgrade, Serbia;
4
Institute of Medical Chemistry, Faculty of
Medicine, University of Belgrade, Belgrade, Serbia
A R T I C L E H I S T O R Y
Received: March 02, 2018
Revised: July 16, 2018
Accepted: July 19, 2018
DOI:
10.2174/0929867325666180904124733
Abstract: Lithium is the smallest monovalent cation with many different biological effects.
Although lithium is present in the pharmacotherapy of psychiatric illnesses for decades, its
precise mechanism of action is still not clarified. Today lithium represents first-line therapy
for bipolar disorders (because it possesses both antimanic and antidepressant properties) and
the adjunctive treatment for major depression (due to its antisuicidal effects). Beside, lithium
showed some protective effects in neurological diseases including acute neural injury, chronic
degenerative conditions, Alzheimer's disease as well as in treating leucopenia, hepatitis and
some renal diseases. Recent evidence suggested that lithium also possesses some anticancer
properties due to its inhibition of Glycogen Synthase Kinase 3 beta (GSK
3
β) which is in-
cluded in the regulation of a lot of important cellular processes such as: glycogen metabolism,
inflammation, immunomodulation, apoptosis, tissue injury, regeneration etc.
Although recent evidence suggested a potential utility of lithium in different conditions, its
broader use in clinical practice still trails. The reason for this is a narrow therapeutic index of
lithium, numerous toxic effects in various organ systems and some clinically relevant interac-
tions with other drugs. Additionally, it is necessary to perform more preclinical as well as
clinical studies in order to a precise therapeutic range of lithium, as well as its detailed
mechanism of action. The aim of this review is to summarize the current knowledge concern-
ing the pharmacological and toxicological effects of lithium.
Keywords: Lithium, pharmacological effects, mechanism of action of lithium, mechanism of action of lithium in
the brain, lithium in preclinical and clinical studies, adverse effects of lithium, drug interactions with lithium.
1. INTRODUCTION
Lithium is the smallest monovalent cation with a lot
of different biological effects. Although recent experi-
mental animal studies showed that lithium represents
an essential nutrient, there is still no consensus regard-
ing optimum lithium concentration. On the other hand,
*Address correspondence to this author at the Department of Phar-
macology, Clinical Pharmacology and Toxicology, Faculty of
Medicine, University of Belgrade, Belgrade, Serbia;
Tel: 381-11-3643-384; Fax: + 381-11-3643-397;
E-mail: brankicamedic@gmail.com
an increase in the level of lithium over 1.2 mM in the
blood causes acute toxicity (nausea, diarrhea, trembling
etc.), and the death may occur above 2 mM. The lack
of therapeutic range of lithium could be explained by
the still unknown mechanisms of action and the lack of
lithium specific targets. Clinical use of lithium has
been limited due to its narrow therapeutic index and
toxic effects in various organ systems. However, lith-
ium has been used in clinical practice for decades [1-4].
The digestive absorption of lithium is complete and
the maximum plasma concentration is observed two to
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Current Medicinal Chemistry, 2020, 27, 337-351
337
REVIEW ARTICLE
Lithium - Pharmacological and Toxicological Aspects: The Current
State of the Art