Lithium biochemical mechanism

Lithium is a fascinating example of an element, that was originally considered a chemical laboratory curiosity, but finally found to be an ultratrace element which in all probability is essential to humans. Moreover, it became a potent and safe drug, with specific effects mainly in the treatment of manic-depressive illness, and also a valuable versatile industrial material with a well-established broad spectrum of applications and possibilities for further developments. The importance of lithium will increase, for example by the discovery of lithium-dependent enzymes, proteins or hormones, the resolution of its biochemical mechanism in affective disorders, and progress in the battery sector, in the nuclear technology, or with the aluminum electrolysis (Schafer 1995, 2000). 

The tissues and cells of experimental animals have been used to investigate the effects of lithium and its biochemical mechanisms. However, it must be pointed out that much of this experimentally derived information may not be extrapolated directly to humans. 

Pharmacologically, lithium as a drug does not lose its efficacy, and does not induce addiction or dependence. Consequently, lithium retains its full effect even if it has been administered for long periods (even years). Moreover, both the effects and side effects of lithium are completely reversible indeed, a mechanical switch-on and -off function of lithium s biochemical mechanism has been discussed, though the details of this remain unknown (Schafer 1998,... 

Schou M. Possible mechanisms of action of lithium salts approaches and perspectives. Biochem Soc Trans 1973 1 81. 

In lithium treated subjects, there is no evidence of reduced bone mass at any of the measured sites in relation to that of control subjects. The mechanism responsible for the maintenance of bone mass despite biochemical evidence of hyperparathyroidism is not clear [45]. We suspect that it is due to renal calcium retention. Indeed, in dogs lithium administration for only 3 days causes a striking decrease in urinary calcium excretion which is independent of the presence of parathyroid hormone and occurs despite the concurrent development of metabolic acidosis [Batlle D, Arruda J, and Kurtzman NA 1981 unpublished observations]. 

Thyroid dysfunction continues to be an infrequent and unpredictable complication found in only 3% of patients according to one review (47 ) and occurring more often in women. A study of the mechanism of action (50 ) in 17 patients on lithium maintenance therapy involved exploration of the hypothalamic-pituitary-thyroid axis. Fourteen subjects showed an exaggerated thyrotropin response to intravenous thyrotropinreleasing hormone that persisted during lithium therapy. However, only 2 of these patients showed any clinical or biochemical evidence of hypothyroidism both showed a delayed recovery of normal TRH response after discontinuing lithium. 

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