Topiramate does not alter expression in rat brain of enzymes of arachidonic acid metabolism
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 met...
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description | 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.
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.
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.
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. |
doi_str_mv | 10.1007/s00213-005-2189-3 |
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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.
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.
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.</description><identifier>ISSN: 0033-3158</identifier><identifier>EISSN: 1432-2072</identifier><identifier>DOI: 10.1007/s00213-005-2189-3</identifier><identifier>PMID: 15719218</identifier><identifier>CODEN: PSYPAG</identifier><language>eng</language><publisher>Berlin: Springer</publisher><subject>Administration, Oral ; Animals ; Anticonvulsants. Antiepileptics. Antiparkinson agents ; Arachidonic Acid - metabolism ; Biological and medical sciences ; Blotting, Western ; Body Weight - drug effects ; Brain - drug effects ; Brain - enzymology ; Fructose - administration & dosage ; Fructose - analogs & derivatives ; Fructose - pharmacology ; Immunoenzyme Techniques ; Leptin - blood ; Male ; Medical sciences ; Neuropharmacology ; Pharmacology. Drug treatments ; Phospholipases A - metabolism ; Phospholipases A2 ; Prostaglandin-Endoperoxide Synthases - metabolism ; Rats ; Rats, Inbred F344 ; Time Factors</subject><ispartof>Psychopharmacologia, 2005-07, Vol.180 (3), p.523-529</ispartof><rights>2005 INIST-CNRS</rights><rights>Springer-Verlag 2005</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-487ff04df0e1e923c085c6c59b545a785c81dff993029039907af8f4050f34223</citedby><cites>FETCH-LOGICAL-c387t-487ff04df0e1e923c085c6c59b545a785c81dff993029039907af8f4050f34223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16876783$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15719218$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GHELARDONI, Sandra</creatorcontrib><creatorcontrib>BAZINET, Richard P</creatorcontrib><creatorcontrib>RAPOPORT, Stanley I</creatorcontrib><creatorcontrib>BOSETTI, Francesca</creatorcontrib><title>Topiramate does not alter expression in rat brain of enzymes of arachidonic acid metabolism</title><title>Psychopharmacologia</title><addtitle>Psychopharmacology (Berl)</addtitle><description>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.
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.
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.
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.</description><subject>Administration, Oral</subject><subject>Animals</subject><subject>Anticonvulsants. Antiepileptics. Antiparkinson agents</subject><subject>Arachidonic Acid - metabolism</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Body Weight - drug effects</subject><subject>Brain - drug effects</subject><subject>Brain - enzymology</subject><subject>Fructose - administration & dosage</subject><subject>Fructose - analogs & derivatives</subject><subject>Fructose - pharmacology</subject><subject>Immunoenzyme Techniques</subject><subject>Leptin - blood</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neuropharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Phospholipases A - metabolism</subject><subject>Phospholipases A2</subject><subject>Prostaglandin-Endoperoxide Synthases - metabolism</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Time Factors</subject><issn>0033-3158</issn><issn>1432-2072</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkU-LFDEQxYMo7rj6AbxIEPTWWkklk-Qoi_9gwct68hBq0glm6e6MSQ-4--nNOAMLXswlL_B7j6o8xl4KeCcAzPsGIAUOAHqQwroBH7GNUCgHCUY-ZhsAxAGFthfsWWu30I-y6im7ENoI1y0b9uOm7HOlmdbIxxIbX8rKaVpj5fH3vsbWcll4Xnille8qdVUSj8v93dzhLqlS-JnHsuTAKeSRz3GlXZlym5-zJ4mmFl-c70v2_dPHm6svw_W3z1-vPlwPAa1ZB2VNSqDGBFFEJzGA1WEbtNtppcn0hxVjSs4hSAfoHBhKNinQkFBJiZfs7Sl3X8uvQ2yrn3MLcZpoieXQ_Na4DiP8FxQGnEU8Jr7-B7wth7r0Jfzxo5VyqDskTlCopbUak9_XPFO98wL8sR9_6sf3fv7aPHbPq3PwYTfH8cFxLqQDb84AtUBTqrSE3B64rTVb02f8Aw4ylqA</recordid><startdate>20050701</startdate><enddate>20050701</enddate><creator>GHELARDONI, Sandra</creator><creator>BAZINET, Richard P</creator><creator>RAPOPORT, Stanley I</creator><creator>BOSETTI, Francesca</creator><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QR</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20050701</creationdate><title>Topiramate does not alter expression in rat brain of enzymes of arachidonic acid metabolism</title><author>GHELARDONI, Sandra ; BAZINET, Richard P ; RAPOPORT, Stanley I ; BOSETTI, Francesca</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-487ff04df0e1e923c085c6c59b545a785c81dff993029039907af8f4050f34223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Administration, Oral</topic><topic>Animals</topic><topic>Anticonvulsants. Antiepileptics. Antiparkinson agents</topic><topic>Arachidonic Acid - metabolism</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Body Weight - drug effects</topic><topic>Brain - drug effects</topic><topic>Brain - enzymology</topic><topic>Fructose - administration & dosage</topic><topic>Fructose - analogs & derivatives</topic><topic>Fructose - pharmacology</topic><topic>Immunoenzyme Techniques</topic><topic>Leptin - blood</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neuropharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Phospholipases A - metabolism</topic><topic>Phospholipases A2</topic><topic>Prostaglandin-Endoperoxide Synthases - metabolism</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GHELARDONI, Sandra</creatorcontrib><creatorcontrib>BAZINET, Richard P</creatorcontrib><creatorcontrib>RAPOPORT, Stanley I</creatorcontrib><creatorcontrib>BOSETTI, Francesca</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Psychopharmacologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GHELARDONI, Sandra</au><au>BAZINET, Richard P</au><au>RAPOPORT, Stanley I</au><au>BOSETTI, Francesca</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Topiramate does not alter expression in rat brain of enzymes of arachidonic acid metabolism</atitle><jtitle>Psychopharmacologia</jtitle><addtitle>Psychopharmacology (Berl)</addtitle><date>2005-07-01</date><risdate>2005</risdate><volume>180</volume><issue>3</issue><spage>523</spage><epage>529</epage><pages>523-529</pages><issn>0033-3158</issn><eissn>1432-2072</eissn><coden>PSYPAG</coden><abstract>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.
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.
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.
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.</abstract><cop>Berlin</cop><pub>Springer</pub><pmid>15719218</pmid><doi>10.1007/s00213-005-2189-3</doi><tpages>7</tpages></addata></record> |
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subjects | Administration, Oral Animals Anticonvulsants. Antiepileptics. Antiparkinson agents Arachidonic Acid - metabolism Biological and medical sciences Blotting, Western Body Weight - drug effects Brain - drug effects Brain - enzymology Fructose - administration & dosage Fructose - analogs & derivatives Fructose - pharmacology Immunoenzyme Techniques Leptin - blood Male Medical sciences Neuropharmacology Pharmacology. Drug treatments Phospholipases A - metabolism Phospholipases A2 Prostaglandin-Endoperoxide Synthases - metabolism Rats Rats, Inbred F344 Time Factors |
title | Topiramate does not alter expression in rat brain of enzymes of arachidonic acid metabolism |
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