Inositol monophosphatase 1 is an enzyme that in humans is encoded by the IMPA1 gene.[5][6]
IMPA1 has been shown to interact with Bergmann glial S100B[7] and calbindin.[8][9]
L-690,330 is a competitive inhibitor of IMPase activity with very good activity in vitro however with limited bioavailability in vivo.[10] Due to its increased specificity compared to Lithium, L-690,330 has been used extensively in characterizing the results of IMPase inhibition in various cell culture models. L-690,488, a prodrug or L-690,330, has also been developed which has greater cell permeability. Treatment of cortical slices with L-690,488 resulted in accumulation of inositol demonstrating the activity of this inhibitor in tissue.[11]
Inhibition of IMPA1 activity can have pleiotropic effects on cellular function, including altering phosphoinositide signalling,[12] autophagy, apoptosis,[13] and other effects.
Initially it was noticed that several drugs useful in treatment of bipolar disorder such as lithium, carbamazepine and valproic acid had a common mechanism of action on enzymes in the phosphatidylinositol signalling pathway[14] and the inositol depletion hypothesis for the pathophysiology of bipolar disorder was suggested. Intensive research has so far not confirmed this hypothesis, partly because lithium can also act on a number of other enzymes in this pathway, complicating results from in vitro studies.