|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0018787,
umls-concept:C0055897,
umls-concept:C0082359,
umls-concept:C0085979,
umls-concept:C0205421,
umls-concept:C0439799,
umls-concept:C1280500,
umls-concept:C1372942,
umls-concept:C1416572,
umls-concept:C1707455,
umls-concept:C1999216
|
|
pubmed:issue |
6
|
|
pubmed:dateCreated |
2009-12-22
|
|
pubmed:abstractText |
Clobutinol has been clinically reported to induce long QT syndrome. To clarify its cardiac electrophysiological properties, we compared effects of clobutinol on the isolated myocardium and anesthetized guinea pig heart with those of a hERG K channel blocker, E-4031. In isolated guinea pig ventricular tissues, clobutinol (3 microM) as well as E-4031 (10-100 nM) prolonged the action potential duration without affecting maximum upstroke velocity, but no further prolongation was observed after application of 30 microM clobutinol. In anesthetized closed-chest guinea pigs, clobutinol (1 and 10 mg/kg, intravenously) and E-4031 (0.01 and 1 mg/kg, intravenously) prolonged the QT interval and duration of the monophasic action potential (MAP) in a dose-dependent manner and at the same time increased the beat-to-beat variability of the MAP duration and reversed use-dependent prolongation of the MAP duration and triangulation of the MAP configuration. These results suggest that clobutinol delayed the ventricular repolarization and increased the proarrhythmic parameters linked to the hERG K channel inhibitor-induced torsade de pointes arrhythmias.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Dec
|
|
pubmed:issn |
1533-4023
|
|
pubmed:author |
|
|
pubmed:issnType |
Electronic
|
|
pubmed:volume |
54
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
552-9
|
|
pubmed:dateRevised |
2010-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:19770670-Action Potentials,
pubmed-meshheading:19770670-Amino Alcohols,
pubmed-meshheading:19770670-Anesthesia,
pubmed-meshheading:19770670-Animals,
pubmed-meshheading:19770670-Antitussive Agents,
pubmed-meshheading:19770670-Blood Pressure,
pubmed-meshheading:19770670-Electric Stimulation,
pubmed-meshheading:19770670-Electrocardiography,
pubmed-meshheading:19770670-Electrophysiological Phenomena,
pubmed-meshheading:19770670-Ether-A-Go-Go Potassium Channels,
pubmed-meshheading:19770670-Female,
pubmed-meshheading:19770670-Guinea Pigs,
pubmed-meshheading:19770670-Halothane,
pubmed-meshheading:19770670-Heart,
pubmed-meshheading:19770670-Heart Rate,
pubmed-meshheading:19770670-Male,
pubmed-meshheading:19770670-Membrane Potentials,
pubmed-meshheading:19770670-Piperidines,
pubmed-meshheading:19770670-Pyridines,
pubmed-meshheading:19770670-Ventricular Function,
pubmed-meshheading:19770670-Ventricular Function, Right
|
|
pubmed:year |
2009
|
|
pubmed:articleTitle |
Clobutinol delays ventricular repolarization in the guinea pig heart: comparison with cardiac effects of HERG K+ channel inhibitor E-4031.
|
|
pubmed:affiliation |
Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Funabashi, Chiba, Japan. akirat@phar.toho-u.ac.jp
|
|
pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|
