Possible Interaction: Arachidonic Acid and Carbamazepine

“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.”

“We hypothesized that, like chronic lithium, chronic CBZ administration to rats would reduce NMDAR-mediated signaling via AA.”

“One hypothesis is that, similar to lithium and valproate (antibipolar drugs), carbamazepine might selectively decrease the kinetics of arachidonic acid (AA) in brain phospholipids.”

“RESULTS Ch onic carbamazepine, c ompared with vehicle, decreased the rate of incorporation of AA-CoA (27%-29%) and turnover of AA (2 5%-27%) but not of DHA-CoA or DHA in brain phospholipids.”

“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.”

“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.”

“CONCLUSIONS Ca bamazepine do wnregulates cytosolic phospholipase A(2)-mediated release of ara chidonic acid an d its subsequent conversion to prostaglandin E(2) by cyclooxygenase.”