Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1994-6-16
pubmed:abstractText
BW619C89 [4-amino-2-(4-methyl-1-piperazinyl)-5-(2,3,5- trichlorophenyl)pyrimidine is a use-dependent blocker of voltage-dependent sodium channels that blocks veratrine-induced glutamate release in vitro. The aim of this study is to determine if BW619C89 inhibits glutamate release and is neuroprotective in cerebral ischemia produced by proximal middle cerebral artery (MCA) occlusion in rats. Infarct volume was determined at 24 hr after permanent MCA occlusion from 2,3,5-triphenyltetrazolim hydrochloride-stained sections. Pretreatment with BW619C89 (10, 20, 30 and 50 mg/kg i.v. of mesylate salt) decreased infarct volume in a dose-dependent fashion maximal at 30 mg/kg compared to saline controls. Treatment with 30 mg/kg up to 45 min after MCA occlusion also was effective. Microdialysate glutamate in rats treated with 30 mg/kg of drug before MCA occlusion was decreased in both caudate (ischemic core) and rostral cortex (penumbra) compared to controls. BW619C89 did not induce significant arterial hypotension, except when it was administered by rapid bolus administration. In this case, the hypotension was transient and did not reduce efficacy or superficial cortical blood flow. BW619C89 did not induce the 72 kD heat shock protein in cingulate gyrus or retrosplenial cortex as did MK801, suggesting that BW619C89 does not injure neurons in these regions as do N-methyl-D-aspartate antagonists. These results suggest that inhibition of glutamate release by BW619C89 may be an effective and nontoxic treatment for stroke.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
854-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Neuroprotective effects of a use-dependent blocker of voltage-dependent sodium channels, BW619C89, in rat middle cerebral artery occlusion.
pubmed:affiliation
Department of Neurology, University of California, San Francisco.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't