.A comparison of the ability of myo-inositol and epi-inositol to attenuate lithium-plocarpine seizures in rats Academic Article uri icon

abstract

  • A major hypothesis for the mechanism of action of lithium suggests that lithium affects cellular signalling in neuronal systems linked to the phosphatidylinositol (PI) cycle. Activation of phospholipase C (PLC) results in the cleavage of phosphatidylinositol 4, 5-bisphosphate (PIP2) and the production of two second messengers, inositol trisphosphate (IP3) and diacylglycerol. Lithium uncompetitively inhibits inositol monophosphatase in rat brain (Hallcher and Sherman 1980) and in erythrocytes of bipolar patients (Moscovich et al 1990), elevating levels of inositol monophosphate and reducing the level of inositol in the rat cortex (Allison and Stewart 1971; Sherman et al 1985). Cholinergic stimulation in animals that have been pretreated with a therapeutic dose of lithium elicits a reduction of rnyo-inositol levels and buildup of inositol monophosphate that are tenfold greater than the effects of either the cholinergic agonist or lithium alone (Honchar et al 1983); however, the ability of lithium to significantly affect inositol levels after chronic treatment has been questioned (Sherman et al 1981; Whitworth and Kendall 1989). Several in vitro electrophysiologic and pharmacologic effects of lithium were reversed by myo-inositol, but not by epi-inositol (Busa and Gimiich 1989; Mason and Biello 1992). Reversal of several lithium-induced behaviors, such as inhibition of rearing (Kofman and Belmaker 1990), lithium-pilocarpine seizures

publication date

  • May 1, 1996