Linked Life Data

16278312

Source:http://linkedlifedata.com/resource/pubmed/id/16278312

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-2-23
pubmed:abstractText
The purpose of the present study was to comparatively evaluate human HERG currents and QT intervals following challenge with suspected torsadogenic and nontorsadogenic drugs. Various concentrations of 14 different drugs were initially evaluated in terms of their relative potency to block I(HERG) in stably transfected human embryonic kidney cells. Four general categories of drugs were identified: high-potency blockers (IC50 < 0.1 microM) included lidoflazine, terfenadine, and haloperidol; moderate-potency blockers (0.1 microM < IC50 < 1 microM) included sertindole, thioridazine, and prenylamine; low-potency blockers (IC50 > 1 microM) included propafenone, loratadine, pyrilamine, lovastatin, and chlorpheniramine; and ineffective blockers (IC50 > 300 microM) included cimetidine, pentamidine, and arsenic trioxide. All measurements were performed using similar conditions and tested acute drug effects only (<30 min of drug exposure per measurement). Since two of the drugs that were ineffective I(HERG) blockers, arsenic trioxide and pentamidine, have been associated with cardiac repolarization delays (QT interval lengthening) and torsades de pointes ventricular arrhythmias in patients, we chose to evaluate them further using the isolated perfused rabbit heart model. Neither arsenic trioxide nor pentamidine had any significant effect on QT intervals in this model, even at relatively high (micromolar) concentrations. Similar results were obtained for loratadine in this model. When the hearts were challenged with a known torsadogenic drug such as cisapride, significant QT lengthening was rapidly induced. These results demonstrate that arsenic trioxide and pentamidine are essentially devoid of direct acute effects on cardiac repolarization or inhibition of I(HERG).
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Arsenicals, http://linkedlifedata.com/resource/pubmed/chemical/ERG1 potassium channel, http://linkedlifedata.com/resource/pubmed/chemical/Ether-A-Go-Go Potassium Channels, http://linkedlifedata.com/resource/pubmed/chemical/Haloperidol, http://linkedlifedata.com/resource/pubmed/chemical/Loratadine, http://linkedlifedata.com/resource/pubmed/chemical/Lovastatin, http://linkedlifedata.com/resource/pubmed/chemical/Methadone, http://linkedlifedata.com/resource/pubmed/chemical/Oxides, http://linkedlifedata.com/resource/pubmed/chemical/Pentamidine, http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channel Blockers, http://linkedlifedata.com/resource/pubmed/chemical/Terfenadine, http://linkedlifedata.com/resource/pubmed/chemical/arsenic trioxide
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
316
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1098-106
pubmed:dateRevised
2008-10-28
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Comparative evaluation of HERG currents and QT intervals following challenge with suspected torsadogenic and nontorsadogenic drugs.
pubmed:affiliation
Department of Pharmacology, Georgetown University Medical Center, Washington, DC, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural