Lithium actions/effects

Newer uses have appeared in the treatment of viral diseases including AIDS, alteration of the immune response, and cancer. The lithium salt of 7-linolenic acid (LiGLA) has a significant anticancer effect against certain cancers. The neurochemical basis for lithium action is difficult to define. Lithium carbonate induces a wide range of intra- and extracellular changes—most emphasis has been naturally on the similarities with Na/K/Ca/Mg ions. Lithium selectively interferes with the inositol lipid cycle, representing a unified hypothesis of action. The biochemistry, distribution, and cellular localization of lithium has been extensively documented. 

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... 

Manji HK, Hsiao JK, Risby ED, et al The mechanisms of action of lithium, I effects on serotoninergic and noradrenergic systems in normal subjects. Arch Gen Psychiatry 48 505-512, 1991a... 

Lithium salts are used in the treatment of bipolar affective disorder (i.e., manic depression) and occasionally in mania (but its slow onset of action is somewhat of a disadvantage in this case). Its mechanism of action is still open to debate, but lithium has effects on brain monoamines, on neuronal transmembrane sodium flux, and on cellular phosphatidylinositides related to second messenger systems. Lithium is administered in two salt forms, lithium carbonate (8.98) and lithium citrate (8.99). Side effects are common and include diarrhea, kidney failure, and drowsiness with tremor. 

Selenium and selenium compounds are also used in electroless nickel-plating baths, delayed-action blasting caps, lithium batteries, xeroradiography, cyanine- and noncyanine-type dyes, thin-film field effect transistors (FET), thin-film lasers, and fire-resistant functional fluids in aeronautics (see... 

Lithium. In the lithium carbonate treatment of certain psychotic states, a low incidence (3.6%) of hypothyroidism and goiter production have been observed as side effects (6,36) (see Psychopharmacologicalagents). It has been proposed that the mechanism of this action is the inhibition of adenyl cyclase. Lithium salts have not found general acceptance in the treatment of hyperthyroidism (see Lithiumand lithium compounds). 

The first mood stabilizer was lithium (its antimanic action being discovered in 1948) more recently the anticonvulsant drugs carbamazepine and valproate have been found to be effective in acute mania. Unfortunately these mood stabilizers are only successful in controlling mania to a limited extent and few patients are well enough to leave hospital at the end of 3 weeks of treatment using these drugs as monotherapy. It is increasingly common for combination treatment to be advocated, in which an antipsychotic dmg is combined with lithium or an anticonvulsant. 

In the case of carbamazepine the evidence suggests that its prophylactic efficacy is less than that of lithium (Greil and Kleindienst, 1999). For valproate there is no placebo-controlled evidence as yet to support its efficacy in the prophylaxis of bipolar disorder. The only large-scale study designed to elucidate this action was a failed trial in which neither lithium nor valproate was more effective than placebo in maintenance treatment over 2 years (Bowden et al, 2000). 

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... 

Kinetic resolution can also be accomplished via eliminative pathways. Thus, the enantiomerically enriched allylic alcohol 102 can be prepared from the meso epoxide 96 with up to 96% ee by the action of LDA in the presence of the chiral diamine 101 and 1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU). The DBU is believed to function as an aggregation modifier, and the active catalyst is theorized to be a heterodimer of the lithium amide (deprotonated 101) and DBU, although some nonlinear effects have been observed at low DBU concentrations <00JA6610>. Dipyrrolidino derivatives (e.g., 104) have also demonstrated utility with regard to kinetic resolution <00H1029>. 

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 nature of salt effects in monomolecular heterolysis has been reviewed. The experimental work of the same group on salt effects has continued with a study of the negative salt effect of lithium perchlorate on the heterolysis of 1-iodoadamantane in y-butyrolactone. It is assumed that the salt effect of lithium perchlorate is caused by the salt action on the solvent-separated ion pair of the substrate. 

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