- Publisher Summary This chapter discusses that there is evidence that uptake and metabolism of inositol are of major importance for the provision of phosphatidyl 4,5-bisphosphate (PIP2), the precursor for IP3, and diacylglycerol (DAG). Being a precursor in the phosphoinositide second messenger system, inositol is also an important osmolyte used to regulate the intracellular tonicity during exposure to hypotonic or hypertonic surroundings. This is achieved by inositol release to the extracellular space during hypotonia and enhanced inositol accumulation during hypertonia. It reviews that different facets of the phosphoinositide system are altered by chronic, but not by acute, treatment with drugs that have therapeutic effect in bipolar disorder. Lithium treatment may reduce the efficacy of the phosphoinositide second messenger system by interfering with inositol availability. Direct effects on some components of this system have also been described after chronic treatment with lithium and some of these may be secondary to inositol depletion. Many pharmacological effects of inositol and lithium have been described using the primary cultures of astrocytes or glioma cells. Moreover, noradrenaline and serotonin, two transmitters acting via the phosphoinositide system, have receptors on astrocytes and affect crucial aspects of astrocytic function.