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Mode of Action of Lithium Some Biological Considerations

William E. Bunney Jr, MD; Agu Pert, PhD; Jack Rosenblatt, MD; Candace B. Pert, PhD; Dorothy Gallaper, PhD
Arch Gen Psychiatry. 1979;36(8):898-901. doi:10.1001/archpsyc.1979.01780080072017.
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This communication will review some of the properties of lithium and four possible cellular sites of interaction between lithium and other cations. It will emphasize the observation that lithium interacts with cyclic adenosine monophosphate (AMP)-mediated processes and, finally, will review a hypothesis that the onset of mania may be associated with the development of supersensitivity of catecholamine receptors. New evidence will be reported that lithium can block the development of supersensitivity in CNS neuronal receptors in rats.

PHYSICOCHEMICAL AND TRANSPORT CONSIDERATIONS  The major properties of lithium that determine its actions are size, charge, electrical field density, and energy of hydration. Lithium is the smallest alkali ion. It has the largest electrical field density at its surface and therefore has the largest energy of hydration (energy required to strip off water molecules). Lithium shares many properties with other periodic table group I as well as some group II metals. It competes with four cations most abundant in biological tissue (Na


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