The effects of central nervous system-active valproic acid constitutional isomers, cyclopropyl analogs, and amide derivatives on neuronal growth cone behavior

Valproic acid (VPA) is an effective antiepileptic drug with an additional activity for the treatment of bipolar disorder. It has been assumed that both activities arise from a common target. At the molecular level, VPA targets a number of distinct proteins that are involved in signal transduction. VPA inhibition of ino-sitol synthase reduces the cellular concentration of myo-inosi-tol, an effect common to the mood stabilizers lithium and carbamazepine. VPA inhibition of histone deacetylases acti-vates Wnt signaling via elevated -catenin expression and causes teratogenicity. Given the VPA chemical structure, it may be possible to design VPA derivatives and analogs that mod-ulate specific protein targets but leave the others unaffected. Indeed, it has been shown that some nonteratogenic VPA de-rivatives retain antiepileptic and inositol signaling effects. In thi