INOSITOL MONOPHOSPHATASE - A PUTATIVE TARGET FOR LI+ IN THE TREATMENTOF BIPOLAR DISORDER

Attenuation of the phosphatidylinositol (PI) signal transduction pathw ay as a consequence of inhibition of inositol monophosphatase (IMPase) has been proposed as the mechanism for the efficacy of Li+ in the tre atment of bipolar disorder. Nevertheless, Li+ also affects other aspec ts of PI signal transduction, and it is therefore not clear whether mo dulation of PI responses by Li+ can be attributed solely to inhibition of IMPase. However, inhibitors of IMPase mimic the effects of Li+ on some aspects of PI cell signalling, thus highlighting the potential of IMPase as a target for the treatment of bipolar disorder. The recent description of the three-dimensional structure of IMPase in conjunctio n with site-directed mutagenesis and kinetic studies has led to the el ucidation of the enzyme mechanism. These structural and mechanistic da ta should prove useful in the development of novel inhibitors of IMPas e that might ultimately prove useful clinically.