Divalproex Sodium

Divalproex Sodium binds to and inhibits gamma-aminobutyric acid (GABA) transaminase and its anticonvulsant activity may be exerted by increasing brain concentration of GABA and by inhibiting enzymes that catabolize GABA or block the reuptake of GABA into glia and nerve endings. It also is an HDAC inhibitor. Divalproex Sodium is a stable coordination compound comprised of sodium valproate and valproic acid with anticonvulsant and antiepileptic activities. Divalproex may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels. (In Vitro) :Valproic acid (VPA) (0-15 mM; 24 and 72 h) inhibits Hela cell growth in a dose- and time- dependent manner.Valproic acid (10 mM; 24 h) significantly attenuates the activities of total, cytosol and nuclear HDACs.Valproic acid (0-15 mM; 24 h) induces a G1 phase arrest at 1–3 mM and a G2/M phase arrest at 10 mM, and increases the percentage of sub-G1 cells in HeLa cells. Valproic acid also induces necrosis, apoptosis and lactate dehydrogenase (LDH) release.Valproic acid (0-20 mM; 24 h) activates Tcf/Lef-dependent transcription and synergizes with lithium.Valproic acid (0-5 mM; 0-18 h) increases β-catenin levels in Neuro2A cells.Valproic acid (0-2 mM; 0-24 h) stimulates phosphorylation of AMPK and ACC in hepatocytes.Valproic acid (0-10 mM; 2 days) induces Notch1 signaling and morphologic differentiation, suppresses production of NE tumor markers in SCLC cells. (In Vivo) :Valproic acid (VPA) (500 mg/kg; i.p.; daily for 12 days) inhibits tumor angiogenesis in mice transplanted with Kasumi-1 cells.Valproic acid (350 mg/kg; i.p.; once) enhances social behavior in rats.Valproic acid (0.26% (w/v) ; p.o. via drinking water; 14 days) decreases liver mass, hepatic fat accumulation, and serum glucose in obese mice without hepatotoxicity.