Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical history of lithium began in mid-19th century when it was used to treat gout. It was subsequently administered as a substitute for sodium chloride and towards the end of 1940 its effects for the control of mania were discovered. At present it is used effectively for treatment of mania and for the prophylaxis of bipolar disorder. Though its effect on affective illnesses is evident, the same cannot be said of its mechanism of action, since in spite of the numerous studies performed to date it is still not known exactly how this ion acts. Many theories have been proposed, the most important of which are: normalisation of possible ionic alterations; interactions with the adenylyl cyclase cAMP system; effects on the phosphatidylinositol cycle; stabilisation of the levels of neuroprotective proteins; normalisation of the values of some cytosolic endopeptidases; etc. In any case, it has yet to be determined which of these is the principal factor responsible for lithium's therapeutic action, while at the same time the possibility cannot be totally ruled out that its precise mechanism of action is still to be discovered.
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PMID:[Lithium: 55 years of history in the therapy of bipolar affective disorder]. 1726 94

Bipolar illness is a major psychiatric disorder that affects 1-3% of the worldwide population. Epidemiological studies have demonstrated that this illness is substantially heritable. However, the genetic characteristics remain unknown and a clear personality has not been identified for these patients. The clinical history of lithium began in mid-19th century when it was used to treat gout. In 1940, it was used as a substitute for sodium chloride in hypertensive patients. However, it was then banned, as it had major side effects. In 1949, Cade reported that lithium could be used as an effective treatment for bipolar disorder and subsequent studies confirmed this effect. Over the years, different authors have proposed many biochemical and biological effects of lithium in the brain. In this review, the main mechanisms of lithium action are summarised, including ion dysregulation; effects on neurotransmitter signalling; the interaction of lithium with the adenylyl cyclase system; inositol phosphate and protein kinase C signalling; and possible effects on arachidonic acid metabolism. However, none of the above mechanisms are definitive, and sometimes results have been contradictory. Recent advances in cellular and molecular biology have reported that lithium may represent an effective therapeutic strategy for treating neurodegenerative disorders like Alzheimer's disease, due to its effects on neuroprotective proteins like Bcl-2 and its actions on regulators of apoptosis and cellular resilience, such as GSK-3. However, results are contradictory and more specific studies into the use of lithium in therapeutic approaches for neurodegenerative diseases are required.
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PMID:Lithium: bipolar disorder and neurodegenerative diseases Possible cellular mechanisms of the therapeutic effects of lithium. 1878 69