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August 05, 2007

Lithium: The Lightweight Champion

lithium pelletsLithium is an important drug for the treatment of bipolar illnesses, so named because, the patients have both manic (elated/grandiose/euphoric) and depressive (sad/depressed) features during the course of illnesses. As manic and depressive are at two extremes (poles), manic depressive psychosis is also known as bipolar illness. The discovery of lithium for medical purposes was a serendipity, not only that, a good deal of luck was there in choosing the right dose, as an excess would have been disastrous due to its low therapeutic index.

It is not exactly known as to how it acts. There was speculation that lithium, being a monovalent cation, like sodium ions (Na+), replaced Na+, thereby stopped or inhibited nerve conduction in the brain. Lithium decreases noradrenaline level in the CNS (central nervous system=brain) while increasing the serotonin level. There is a strong correlation between the levels of these neurotransmitters and mood. Lithium could also act by altering the level of glutamate, which acts as an excitatory neurotransmitter in the brain. It might also act by altering gene expression, and this might explain the delay of its onset of action for about a week. Lithium also hinders the regeneration of inositol (a substance necessary for the formation of IP3, an important molecule of the IP3- DAG second messenger system). Presently, the role of lithium in deactivating Glycogen Synthase Kinase enzyme (GSK enzyme, a member of serine/threonine protein kinase family) is implicated as its possible method of action. We all have a 'master clock' in our body, the circadian clock (circa=around, dian =day). A protein named Bmal1 resets this clock. But activated GSK 3B enzyme doesn't let Bmal1 to reset it. Li+, by deactivating GSK3B, brings this clock back into action. But the way it actually acts remains elusive till date. The therapy is not without its attendant risks. Sodium depletion, dehydration, diuretic therapy may augment the risks.

Lithium is also used in batteries (for their high charge density and lightweight: in cell phones, computers), in ceramics (it has a high specific heat capacity), space technology, and was even used in nuclear weapons. No wonder why Kurt Cobain of Nirvana sang his song of praise 'Lithium'.

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