Ethylbutyrate, a valproate-like compound, exhibits inositol-depleting effects - A potential mood-stabilizing drug

Aims: To screen for inositol-depleting valproate-like compounds as potential mood stabilizing drugs. Main methods: We exploited the yeast Saccharomyces cerevisiae, as a model in which inositol de novo synthesis has been extensively characterized, to test the effects of ethyl butyrate (EB), 2-ethyl-butyric acid, sodium butyrate, and n-propyl hexanoate on inositol biosynthesis. Cell growth was followed by measuring the optical density of the cultures (spectrophotometrically). RNA abundance was determined by Northern blot analysis, intracellular inositol was measured by a fluorometric assay, and 1-D-myo-inositol-3-phosphate synthase activity was examined using a chromatographic method. Key findings: Of the tested compounds, only EB exhibited an inositol-depleting effect. The inositol-depleting effect of EB was achieved without significant adverse effect on cell growth, pointing to lesser toxicity compared to valproate. Significance: These results indicate that EB is a potential candidate for mood-stabilizing therapy. (C) 2008 Elsevier Inc. All rights reserved.