Possible Interaction: Arachidonic Acid and Valproic Acid

“BACKGROUND … of chronic valproate (VPA) … arachidonic acid (AA) turnover in brain phospholipids of unanesthetized rats has been ascribed to its inhibition of acyl-CoA synthetase (Acsl)-mediated activation … AA to AA-CoA. Our aim was to identify a rat Acsl isoenzyme that could be inhibited by VPA in vitro.”

“It is based on evidence that chronic administration of lithium, carbamazepine, sodium valproate , or lamotrigine to rats downregulated AA turnover in brain phospholipids, formation of prostaglandin E(2), and/or expression of AA cascade enzymes, including cytosolic phospholipase A(2), cyclooxygenase-2 and/or acyl-CoA synthetase.”

“In shock blood, incubation with VPA significantly reduced collagen-(P = 0.050), arachidonic acid-(P = 0.005), and adenosine diphosphate-(P = 0.023) induced platelet aggregation.”

“In vitro studies … of these, valproic acid (VPA), which …, reduces AA turnover by inhibiting the brain long-chain acyl-CoA synthetase (Acsl)4 mediated acylation of AA to AA-CoA. … whether non-teratogenic VPA analogues might also inhibit Acsl4 catalyzed acylation, and thus have a potential anti-BD action.”

“We hypothesized that valproate (VPA), with mood-stabilizing properties, would also reduce D(2)-like-mediated signaling via AA.”

“ VPA shares many cellular and molecular targets with lithium, including reducing arachidonic acid turnover in rat brain phospholipids and cyclooxygenase-2 (COX-2) protein level and activity in rat brain.”

“RationaleIt has been reported that each of three drugs effective in treating bipolar disorder (lithium, carbamazepine, and valproate ) decreases the turnover of arachidonic acid (AA, 20:4n-6) in brain phospholipids of the awake rat.”

“Because chronic lithium, carbamazepine and valproate decrease the turnover of arachidonic acid (AA) but not docosahexaenoic acid (DHA) in brain phospholipids of the awake rat, we tested if topiramate would produce similar results.”

“The study supports the hypothesis that valproic acid acts in bipolar disorder by reducing the brain arachidonic acid cascade , by inhibiting arachidonoyl–CoA formation.”

“Based on evidence that lithium and valproate , other mood stabilizers, reduce brain arachidonic acid turnover and its conversion via cyclooxygenase to prostaglandin E(2) in rat brain, one possibility is that carbamazepine also targets the arachidonic acid cascade.”