Document Detail


Istaroxime, a first in class new chemical entity exhibiting SERCA-2 activation and Na-K-ATPase inhibition: a new promising treatment for acute heart failure syndromes?
MedLine Citation:
PMID:  19238540     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acute heart failure syndromes (AHFS) are associated with the rapid onset of heart failure (HF) signs and symptoms. Hospitalizations for AHFS continue to rise and are associated with significant mortality and morbidity. Several pharmacological agents are currently approved for the treatment of AHFS, but their use is associated with an increase in short-term mortality. There is a need for new agents that can be given in the acute setting with increased efficacy and safety. Istaroxime is a unique agent with both inotropic and lusitropic properties which is currently being studied for the treatment of AHFS. Istaroxime inhibits the sodium-potassium adenosine triphosphatase (ATPase) and stimulates the sarcoplasmic reticulum calcium ATPase isoform 2 (SERCA-2) thereby improving contractility and diastolic relaxation. Early data from human studies reveal that istaroxime decreases pulmonary capillary wedge pressure (PCWP) and possibly improves diastolic function without causing a significant change in heart rate (HR), blood pressure, ischemic or arrhythmic events. Most commonly reported side effects were related to gastrointestinal intolerance and were dose related. In conclusion, istaroxime is a novel agent being investigated for the treatment of AHFS whose mechanism of action and cellular targets make it a promising therapy. Further studies with longer infusion times in patients with hypotension are required to confirm its efficacy and safety.
Authors:
Hashim Khan; Marco Metra; John E A Blair; Mark Vogel; Matthew E Harinstein; Gerasimos S Filippatos; Hani N Sabbah; Herve Porchet; Giovanni Valentini; Mihai Gheorghiade
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2009-02-24
Journal Detail:
Title:  Heart failure reviews     Volume:  14     ISSN:  1573-7322     ISO Abbreviation:  Heart Fail Rev     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-05     Completed Date:  2010-02-25     Revised Date:  2012-07-12    
Medline Journal Info:
Nlm Unique ID:  9612481     Medline TA:  Heart Fail Rev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  277-87     Citation Subset:  IM    
Affiliation:
Northwestern University, Chicago, IL 60611, USA.
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Animals
Cardiotonic Agents / administration & dosage,  pharmacology*,  therapeutic use*
Dobutamine / pharmacology
Etiocholanolone / administration & dosage,  analogs & derivatives*,  pharmacology,  therapeutic use
Heart Failure / drug therapy*
Hemodynamics / drug effects
Humans
Pulmonary Wedge Pressure / drug effects
Sarcoplasmic Reticulum Calcium-Transporting ATPases / drug effects*
Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/3-((2-aminoethoxy)imino)androstane-6,17-dione; 0/Cardiotonic Agents; 34368-04-2/Dobutamine; 53-42-9/Etiocholanolone; EC 3.6.3.8/ATP2A2 protein, human; EC 3.6.3.8/Sarcoplasmic Reticulum Calcium-Transporting ATPases; EC 3.6.3.9/Sodium-Potassium-Exchanging ATPase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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