Inositol monophosphatase, the putative therapeutic target for lithium

Abstract

Lithium has been hypothesised to exert its therapeutic effects in the treatment of bipolar disorder by attenuating phosphatidylinositol (PI) cell signalling pathways that are presumably hyperactive in this disorder. More specifically, lithium has been proposed to inhibit inositol monophosphatase (IMPase) thereby causing a depletion of intracellular inositol which results in a reduction in the synthesis of the PI required to sustain this signalling pathway. In the present article this 'inositol depletion' hypothesis will be reviewed and pathological, pharmacodynamic, developmental and anatomical aspects of IMPase as well as inhibitors of this enzyme will be described.