Pharmacological profile of the new inotropic agent AT-11

An Sheng Lee, Tian Shung Wu, Ming Jai Su

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Although there are many classes of drugs, including cardiac glycosides, sympathomimetic inotropes, β-adrenergic antagonists, angiotensin-converting enzyme inhibitors (ACE inhibitors) and spironolactone etc. used for the treatment of heart failure, the morbidity and mortality rates of patients after these treatments are not ameliorated. Chronic administration of Sympathomimetic inotropes also increased the arrhythmogenic effects. Consequently, improvement of treatment for heart failure remains a major medical challenge for the coming years. In this present experiment, the novel Na+-K+ ATPase inhibitor AT-11 was characterized for its inotropic and toxic properties. Comparing AT-11 with ouabain, we found that AT-11 concentration-dependently increased contractility in guinea pig heart preparations, and the safety index of AT-11 was better than ouabain in vitro. In the in vivo study, AT-11 was also safer than ouabain at the equieffective dose. Moreover, AT-11 slowed heart rate more than ouabain did. This may be due to a larger AT-11-induced increase in vagal reflex than with ouabain and an indirect decrease in sympathetic tone to prevent Ca2+ overload.

Original languageEnglish
Pages (from-to)224-230
Number of pages7
JournalEuropean Journal of Pharmacology
Volume580
Issue number1-2
DOIs
Publication statusPublished - 2008 Feb 2

All Science Journal Classification (ASJC) codes

  • Pharmacology

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