L-690,330 is a competitive inhibitor of IMPase activity with very good activity
in vitro however with limited
bioavailabilityin 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]
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.
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