Topiramate does not alter expression in rat brain of enzymes of arachidonic acid metabolism.
BACKGROUND
When administered chronically to rats, drugs that are effective in bipolar disorder-lithium and the anticonvulsants, valproic acid and carbamazepine-have been shown to downregulate the expression of certain enzymes involved in brain arachidonic acid (AA) release and cyclooxygenase (COX)-mediated metabolism. Phase II clinical trials with the anticonvulsant topiramate [2,3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate] suggest that this drug may also be effective for bipolar disorder.


OBJECTIVE
To see if topiramate has effects similar to those of the other three drugs, we administered topiramate to rats for 14 days at 20 mg/kg, p.o. twice daily.


RESULTS
Compared with p.o. vehicle, topiramate treatment did not significantly affect the brain activity or protein level of cytosolic phospholipase A2, secretory PLA2, or Ca2+-independent iPLA2. Additionally, brain protein levels of COX-1, COX-2, 5-lipoxygenase, and cytochrome P450 epoxygenase were unchanged.


CONCLUSIONS
These results suggest that topiramate does not modify expression of the enzymes involved in brain AA metabolism that have been shown to be targeted by lithium, valproic acid, or carbamazepine. If topiramate proves effective in bipolar disorder, it may not act by modulating brain AA metabolism. In view of the proven anticonvulsant effect of topiramate, our results also suggest that the AA cascade is not involved in the anti-seizure properties of the drug.
Ghelardoni
Sandra
S
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, 9000 Rockville Pike, Bldg. 10, Rm. 6N202, Bethesda, MD 20892, USA.
Bazinet
Richard P
RP
Rapoport
Stanley I
SI
Bosetti
Francesca
F
D000284:Administration, Oral; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D020738:Leptin / Q000097:blood; D008297:Male; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D000077236:Topiramate
D020738:Leptin; D000077236:Topiramate; D016718:Arachidonic Acid; D005632:Fructose; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2
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