Linked Life Data

15831442

Source:http://linkedlifedata.com/resource/pubmed/id/15831442

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-6-20
pubmed:abstractText
The present study characterized the effects of TS-011 [N-(3-chloro-4-morpholin-4-yl) phenyl-N'-hydroxyimido formamide], a new selective inhibitor of the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE), on the metabolism of arachidonic acid by human and rat renal microsomes and the inhibitory effects of this compound on hepatic cytochrome P450 enzymes involved in drug metabolism. The effects of TS-011 on the fall in cerebral blood flow following subarachnoid hemorrhage (SAH) and in reducing infarct size in ischemic stroke models were also examined since 20-HETE may contribute to the development of cerebral vasospasm. TS-011 inhibited the synthesis of 20-HETE by human renal microsomes and recombinant CYP4A11 and 4F2, 4F3A, and 4F3B enzymes with IC50 values around 10 to 50 nM. It had no effect on the activities of CYP1A, 2C9, 2C19, 2D6, or 3A4 enzymes. TS-011 inhibited the synthesis of 20-HETE by rat renal microsomes with an IC50 of 9.19 nM, and it had no effect on epoxygenase activity at a concentration of 100 microM. TS-011 (0.01-1 mg/kg i.v.) reversed the fall in cerebral blood flow and the increase in 20-HETE levels in the cerebrospinal fluid of rats after SAH. TS-011 also reduced the infarct volume by 35% following transient ischemic stroke and in intracerebral hemorrhage in rats. Injection of 20-HETE (8 or 12 mg/kg) into the carotid artery produced an infarct similar to that seen in the ischemic stroke model. These studies indicate that blockade of the synthesis of 20-HETE with TS-011 opposes cerebral vasospasm following SAH and reduces infarct size in ischemic models of stroke.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
314
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
77-85
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15831442-Alkane 1-Monooxygenase, pubmed-meshheading:15831442-Animals, pubmed-meshheading:15831442-Brain, pubmed-meshheading:15831442-Carotid Arteries, pubmed-meshheading:15831442-Cerebral Hemorrhage, pubmed-meshheading:15831442-Cerebral Infarction, pubmed-meshheading:15831442-Cerebrovascular Circulation, pubmed-meshheading:15831442-Collagenases, pubmed-meshheading:15831442-Formamides, pubmed-meshheading:15831442-Hydroxyeicosatetraenoic Acids, pubmed-meshheading:15831442-Infarction, Middle Cerebral Artery, pubmed-meshheading:15831442-Infusions, Intra-Arterial, pubmed-meshheading:15831442-Isoenzymes, pubmed-meshheading:15831442-Male, pubmed-meshheading:15831442-Morpholines, pubmed-meshheading:15831442-Rats, pubmed-meshheading:15831442-Rats, Inbred SHR, pubmed-meshheading:15831442-Rats, Sprague-Dawley, pubmed-meshheading:15831442-Stroke
pubmed:year
2005
pubmed:articleTitle
Beneficial effects of a new 20-hydroxyeicosatetraenoic acid synthesis inhibitor, TS-011 [N-(3-chloro-4-morpholin-4-yl) phenyl-N'-hydroxyimido formamide], on hemorrhagic and ischemic stroke.
pubmed:affiliation
Medicinal Pharmacology Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama-city, Saitama 331-9530, Japan. noriyuki.miyata@po.rd.taisho.co.jp
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural