Topiramate does not alter the kinetics of arachidonic or docosahexaenoic acid in brain phospholipids of the unanesthetized rat.
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.
Lee
Ho-Joo
HJ
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, 20892, USA.
Ghelardoni
Sandra
S
Chang
Lisa
L
Bosetti
Francesca
F
Rapoport
Stanley I
SI
Bazinet
Richard P
RP
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
D010743:Phospholipids; D000077236:Topiramate; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D005632:Fructose