Lithium has been used for over 60 years as a treatment for manic depressive or  bipolar disorder. The treatment is one of the most effective for the disorder as well as one of the most inexpensive. Bethany Halford surveys the current research on the drugs mechanism of action in this week’s C&EN:

Lithium has a reputation for being moderately effective at treating or preventing bipolar depression. Scientists know that lithium displaces magnesium ions and inhibits at least 10 cellular targets. They have been able to narrow that range on the basis of what lithium inhibits at therapeutically relevant concentrations, roughly 0.6 to 1 mM.

One putative lithium target researchers have been pursuing for decades is inositol monophosphatase, or IMPase. The enzyme is part of the phosphatidylinositol signaling pathway. It strips the phosphate off of inositol phosphate to produce inositol, a key substance in the biosynthesis of compounds that trigger cellular responses.

There is some evidence that in bipolar patients the phosphatidylinositol signaling pathway becomes hyperactive. Inhibiting IMPase halts the pathway and depletes inositol. Adding credence to this theory, researchers have fingered inositol depletion in the mechanisms of two other bipolar medications—carbamazepine (Tegretol) and divalproex (Depakote), also called valproic acid.

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