title: Topiramate does not alter the kinetics of arachidonic or docosahexaenoic acid in brain phospholipids of the unanesthetized rat.
abstract: Interest in the potential therapeutic utility of topiramate for treating bipolar disorder was stimulated by published reports of investigator-initiated open label clinical studies. 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. Rats received either topiramate (20 mg/kg twice per day) or vehicle for 14 days and then while unanesthetized were infused intravenously with either [1-(14)C] AA or [1-(14)C] DHA for 5 min while blood was collected from the femoral artery at fixed times. Topiramate did not alter the incorporation rate of AA or DHA from their respective brain acyl-CoA pool into brain phospholipids, nor the turnover of AA and DHA in brain phospholipids. The results of our study indicate that topiramate does not possess a pharmacological property that three drugs with proven efficacy in treating bipolar disorder have in common.
authors.affiliation: Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Ho-Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Sandra
authors.initials: S
authors.lastname: Ghelardoni
authors.forename: Lisa
authors.initials: L
authors.lastname: Chang
authors.forename: Francesca
authors.initials: F
authors.lastname: Bosetti
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Rapoport
authors.forename: Richard P
authors.initials: RP
authors.lastname: Bazinet
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000097:blood / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000097:blood / Q000378:metabolism*; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D000077236:Topiramate
chemical_list: D010743:Phospholipids; D000077236:Topiramate; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D005632:Fructose