Linked Life Data

7714775

Source:http://linkedlifedata.com/resource/pubmed/id/7714775

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1995-5-17
pubmed:abstractText
The Ca(++)-activated K+ (Gardos) channel of erythrocytes plays a crucial role in K+ loss and dehydration of sickle erythrocytes; a potential therapeutic strategy would be to prevent dehydration by specifically blocking this channel. The authors report here on the activity of the clotrimazole (CLT) metabolite, 2-chlorophenyl-bis-phenyl-methanol, which accounts for a portion of the blockade of the erythrocyte Gardos channel when CLT is given orally to normal volunteers. Administration of a single oral dose of 1 g of CLT to four normal healthy volunteers (approximately 15 mg/kg of body weight) resulted in 51% to 92% peak inhibition of the Gardos channel measured in whole blood 2 to 4 hr later. Inhibition remained detectable for 24 to 34 hr. Inhibition of the Gardos channel correlated best with the summed levels of CLT plus its two major metabolites (P < .002; apparent IC50 = 0.65 +/- 0.19 microM). In vitro experiments with 2-chlorophenyl-bis-phenyl-methanol revealed dose-dependent inhibition of K transport and displacement of specifically bound 125I-charybdotoxin. Thus, the imidazole ring of CLT, which is required for antimycotic activity and associated with most of the historically observed toxicity, is not necessary for inhibition of the Gardos channel.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
266-72
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Oral administration of clotrimazole and blockade of human erythrocyte Ca(++)-activated K+ channel: the imidazole ring is not required for inhibitory activity.
pubmed:affiliation
Department of Pathology, Children's Hospital, Boston, Massachusetts, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.