Ethylbutyrate, a valproate-like compound, exhibits inositol-depleting effects--a potential mood-stabilizing drug.
OBJECTIVE
To screen for inositol-depleting valproate-like compounds as potential mood stabilizing drugs.


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.


RESULTS
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.


CONCLUSIONS
These results indicate that EB is a potential candidate for mood-stabilizing therapy.
Azab
Abed N
AN
Department of Biological Sciences, Wayne State University, 5047 Gullen Mall, Detroit, Michigan 48202, USA. azab@bgu.ac.il
Mehta
Dhara V
DV
Chesebro
John E
JE
Greenberg
Miriam L
ML
D000339:Affect / Q000187:drug effects*; D001714:Bipolar Disorder / Q000188:drug therapy; D002087:Butyrates / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007294:Inositol / Q000032:analysis*; D019753:Intramolecular Lyases / Q000037:antagonists & inhibitors; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology*
D002087:Butyrates; D007294:Inositol; D014635:Valproic Acid; D019753:Intramolecular Lyases; C105497:D-myo-inositol-3-phosphate synthase; C045572:ethyl butyrate