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rdf:type |
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lifeskim:mentions |
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0034693,
umls-concept:C0046616,
umls-concept:C0205234,
umls-concept:C0205245,
umls-concept:C0205374,
umls-concept:C0205494,
umls-concept:C0220781,
umls-concept:C0332161,
umls-concept:C0549178,
umls-concept:C0917798,
umls-concept:C1274040,
umls-concept:C1615056,
umls-concept:C1883254
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pubmed:issue |
4
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pubmed:dateCreated |
2007-11-5
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pubmed:abstractText |
TS-011, a potent and selective inhibitor of 20-HETE synthesis, has been described as providing significant benefits in animal stroke models. However, no studies have investigated changes in brain 20-HETE levels after cerebral ischemia. Also lacking are studies of TS-011 pharmacodynamics with respect to brain 20-HETE levels that may explain the benefits of TS-011 in animal models of ischemic stroke. The present study sought to explore changes in 20-HETE levels in brain tissue, as well as in plasma, after a 90-min episode of transient focal cerebral ischemia. Pharmacodynamics of TS-011 were also examined. Then, we evaluated the long-term effects of TS-011 when administered as in this pharmacodynamics study. The major findings of the present study are as follows: (1) brain 20-HETE levels increased significantly within 7.5h after MCAO; (2) TS-011 at doses of 0.1 and 0.3mg/kg administered at regular 6-h intervals appeared to reduce brain 20-HETE levels continuously; (3) TS-011 when administered as in this pharmacodynamics study improved long-term neurological and functional outcomes. These findings strongly suggest that 20-HETE plays an important role in the development of neurological and functional deficits after focal cerebral ischemia and that TS-011 may provide benefits in patients suffering ischemic stroke.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0168-0102
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
59
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
475-80
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pubmed:meshHeading |
pubmed-meshheading:17933409-Animals,
pubmed-meshheading:17933409-Brain,
pubmed-meshheading:17933409-Brain Ischemia,
pubmed-meshheading:17933409-Cerebral Arteries,
pubmed-meshheading:17933409-Cerebrovascular Circulation,
pubmed-meshheading:17933409-Dose-Response Relationship, Drug,
pubmed-meshheading:17933409-Drug Administration Schedule,
pubmed-meshheading:17933409-Formamides,
pubmed-meshheading:17933409-Hydroxyeicosatetraenoic Acids,
pubmed-meshheading:17933409-Ischemic Attack, Transient,
pubmed-meshheading:17933409-Morpholines,
pubmed-meshheading:17933409-Neuroprotective Agents,
pubmed-meshheading:17933409-Rats,
pubmed-meshheading:17933409-Rats, Sprague-Dawley,
pubmed-meshheading:17933409-Treatment Outcome,
pubmed-meshheading:17933409-Up-Regulation,
pubmed-meshheading:17933409-Vasodilation
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pubmed:year |
2007
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pubmed:articleTitle |
Continuous inhibition of 20-HETE synthesis by TS-011 improves neurological and functional outcomes after transient focal cerebral ischemia in rats.
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pubmed:affiliation |
Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co Ltd, Saitama, Japan. yu.tanaka@po.rd.taisho.co.jp
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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