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The high affinity inositol transport system – implications for the pathophysiology and treatment of bipolar disorder
Author(s) -
Calker Dietrich van,
Belmaker Robert H
Publication year - 2000
Publication title -
bipolar disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.285
H-Index - 129
eISSN - 1399-5618
pISSN - 1398-5647
DOI - 10.1034/j.1399-5618.2000.020203.x
Subject(s) - inositol , lithium (medication) , downregulation and upregulation , treatment of bipolar disorder , chemistry , mood stabilizer , carbamazepine , mechanism of action , mood , mechanism (biology) , in vitro , endocrinology , pharmacology , medicine , neuroscience , bipolar disorder , psychology , biochemistry , mania , receptor , biology , psychiatry , epilepsy , gene , philosophy , epistemology
The ‘inositol‐depletion hypothesis’ postulates that the therapeutic effects of lithium are due to inhibition of inositol monophosphatase, which leads to depletion of brain cells of myo‐inositol and consequently to dampening of phosphoinositide (PI) signaling. This article examines the potential relevance of an alternative mechanism for inositol depletion: inhibition of myo‐inositol uptake that proceeds via the sodium/myo‐inositol cotransport (SMIT). We discuss recent in vitro experiments that show a pronounced downregulation of SMIT after chronic treatment with lithium, carbamazepine, and valproate at therapeutically relevant concentrations. It is concluded that downregulation of SMIT could represent a common mechanism of action of mood stabilizers.