Lithium mechanisms of action

Lithium Mechanism of action uncertain suppresses inositol signaling and inhibits glycogen synthase kinase-3 (GSK-3), a multifunctional protein kinase No significant antagonistic actions on autonomic nervous system receptors or specific CNS receptors no sedative effects Bipolar affective disorder-prophylactic use can prevent mood swings between mania and depression Oral absorption, renal elimination half-life 20 h. narrow therapeutic window (monitor blood levels) Toxicity Tremor, edema, hypothyroidism, renal dysfunction, dysrhythmias pregnancy category D Interactions Clearance decreased by thiazides and some NSAIDs... 

Mechanism of Action Lithium s pharmacologic mechanism of action is not well understood and probably involves multiple effects. Possibilities include altered ion transport, increased intraneuronal catecholamine metabolism, neuroprotection or increased brain-derived neurotrophic factor, inhibition of second messenger systems, and reprogramming of gene expression.29... 

Mechanism of Action The mechanism of action of divalproex is not well understood. It is known to affect ion transport and enhances the activity of y-aminobutyric acid. Like lithium, it also has possible neuroprotective effects through enhancement of brain-derived neurotrophic factor.31... 

Jope RS. Anti-bipolar therapy Mechanism of action of lithium. Mol Psych 1999 4 117-128. 

Post RM, Ciark M, Chuang DM, Hough C, Li H. Lithium Carbamaze-pine, and Valproate in Affective Illness Biological and Neurobiological Mechanisms in Bipolar Medications Mechanisms of Action. Manji HK, Bowden CL, Belmaker RH Eds. Washington DC, Am Psychiatric Press 2000 219-248. 

Lithium, while not required for life, is used therapeutically in the form of lithium carbonate for the treatment of manic depression although its mechanism of action remains a mystery. Effective treatment requires attaining serum lithium concentrations of between 0.8 and 1.2 mmol/L. 

The mechanism of action of U ions remains to be fully elucidated. Oiemi-cally, lithium is the lightest of the alkaU metals, which include such biologically important elements as sodium and potassium. Apart from interference with transmembrane cation fluxes (via ion channels and pumps), a lithium effect of major significance appears to be membrane depletion of phosphatidylinositol bisphosphates, the principal lipid substrate used by various receptors in transmembrane signalling (p. 66). 

Its mechanism of action is not well understood. Some possible actions include inhibition of norepinephrine release and increased re-uptake of norepinephrine and serotonin. It also possibly increases the synthesis and turnover of serotonin. Lithium interferes with the production and release of the second messengers phosphatdylinositol-4,5-bisphosphate and diacyl glycerol. Finally it may uncouple receptor recognition sites from GTP-binding protein by competing with Mg++. 

Lithium is effective in the treatment of mood disorders. Its mechanism of action is unclear but is likely to be via modification of intracellular second... 

Preclinical studies examining the mechanism of action of mood stabilizers has extended research attention in the neurobiology of BD from a focus on biogenic amines to include study of the second messenger systems. These studies have found that chronic lithium treatment at therapeutic levels in adult rats alters ac-... 

In this chapter we review the mechanisms of action, pharmacokinetics, side effects, and uses of lithium and the anticonvulsants as they apply to child psychiatric clinical practice. 

Lenox, R.H. and Hahn, C.G. (2000) Overview of the mechanism of action of lithium in the brain fifty-year update. / Clm Psychiatry 61 5-15. 

Andersen PH The dopamine uptake inhibitor GBR 12909 selectivity and molecular mechanism of action. Fur J Pharmacol 166 493-504, 1989 Andersen PH, Geisler A Lithium inhibition of forskohn-stimulated adenylate... 

---