Valnoctamide a non-teratogenic amide derivative of valproic acid inhibits arachidonic acid activation in vitro by recombinant acyl-CoA synthetase-4

摘要

ObjectiveValproic acid (VPA), a mood stabilizer used for treating bipolar disorder (BD), uncompetitively inhibits acylation of arachidonic acid (AA) by recombinant AA-selective acyl-CoA synthetase (Acsl)-4 at Ki of 25 mM. Inhibition may account for VPA’s ability to reduce AA turnover in brain phospholipids of unanesthetized rats at a therapeutically relevant dose. VPA is teratogenic. We now tested whether valnoctamide (VCD), a non-teratogenic amide derivative of a VPA chiral isomer, which had antimanic potency in a Phase III BD trial, also inhibits recombinant Acsl4.