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Inositol monophosphatase, the putative therapeutic target for lithium
Authors:John R. Atack
Affiliation:Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK
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.
Keywords:Inositol monophosphatase   Lithium   Inositol   Phosphatidylinositol   Bipolar disorder   Inhibitor   Depression   Mania
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