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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1995-12-7
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pubmed:abstractText |
We studied the effects of NE-10064 (azimilide), a new antiarrhythmic agent reported to be a selective blocker of the slowly activating component of the delayed rectifier, IKs. In ferret papillary muscles, NE-10064 increased effective refractory period (ERP) and decreased isometric twitch tension in a concentration-dependent manner (0.3-30 microM). Increases in ERP showed reverse use-dependence, and were greater at 1 than at 3 Hz. In contrast, changes in tension were use dependent, with larger decreases observed at 3 than at 1 Hz. In guinea pig ventricular myocytes, NE-10064 (0.3-3 microM) significantly prolonged action potential duration (APD) at 1 Hz. At 3 Hz, NE-10064 (0.3-1 microM) increased APD only slightly, and at 10 microM decreased APD and the plateau potential. NE-10064 potently blocked the rapidly activating component of the delayed rectifier, IKr (IC50 0.4 microM), and inhibited IKs (IC50 3 microM) with nearly 10-fold less potency. NE-10064 (10 microM) did not block the inward rectifier potassium current (IKl). NE-10064 (10 microM) blocked the L-type calcium current (ICa) in a use-dependent manner; block was greater at 3 than at 1 Hz. We conclude that (a) NE-10064's block of potassium currents is relatively selective for IKr over IKs, (b) NE-10064 inhibits ICa in a use-dependent fashion, and (c) NE-10064's effects on ERP and tension in papillary muscle as well as APD and action potential plateau level in myocytes may be explained by its potassium and calcium channel blocking properties.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Arrhythmia Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazolidines,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/azimilide
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0160-2446
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
26
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
259-71
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:7475051-Action Potentials,
pubmed-meshheading:7475051-Animals,
pubmed-meshheading:7475051-Anti-Arrhythmia Agents,
pubmed-meshheading:7475051-Calcium,
pubmed-meshheading:7475051-Calcium Channel Blockers,
pubmed-meshheading:7475051-Dose-Response Relationship, Drug,
pubmed-meshheading:7475051-Ferrets,
pubmed-meshheading:7475051-Guinea Pigs,
pubmed-meshheading:7475051-Heart,
pubmed-meshheading:7475051-Imidazoles,
pubmed-meshheading:7475051-Imidazolidines,
pubmed-meshheading:7475051-Male,
pubmed-meshheading:7475051-Piperazines,
pubmed-meshheading:7475051-Potassium Channel Blockers,
pubmed-meshheading:7475051-Refractory Period, Electrophysiological
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pubmed:year |
1995
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pubmed:articleTitle |
Use-dependent effects of the class III antiarrhythmic agent NE-10064 (azimilide) on cardiac repolarization: block of delayed rectifier potassium and L-type calcium currents.
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pubmed:affiliation |
Department of Pharmacology, Merck Research Laboratories, West Point, PA 19486-0004, USA.
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pubmed:publicationType |
Journal Article,
In Vitro
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