Document Detail

Pharmacological and clinical impact of the unique molecular structure of a new plasminogen activator.
MedLine Citation:
PMID:  9447335     Owner:  NLM     Status:  MEDLINE    
Thrombolytic therapy has been recognized as a significant improvement in the management of acute myocardial infarction. Thrombolytic agents however have been limited by short half-lives that necessitate complex administration protocols and by the potential for bleeding complications. The native t-PA molecule has since been modified in an attempt to achieve improved lytic characteristics with less risk of bleeding. Reteplase is a third-generation recombinant mutant of tissue-type plasminogen activator (t-PA) that is expressed in Escherichia coli cells and consists of the kringle 2 and the protease domains of t-PA. Compared with t-PA, reteplase has a lower fibrin binding, which may translate to improved clot penetration. As well as a longer half-life and a more rapid initiation of thrombolysis. Preclinical pharmacology studies have indicated that reteplase has potent in vivo thrombolytic activity and leads to rapid reperfusion; these findings have been confirmed by promising results obtained in large-scale clinical trials. Other new agents developed by modifying the native t-PA molecule include the n-PA and the TNK mutants of t-PA. These novel, genetically modified thrombolytic agents all lyse clots better than the native t-PA; however, they differ with respect to their half-lives and fibrin-binding activity. Although all the third-generation thrombolytic agents have shown considerable potential in improving the efficacy of thrombolytic therapy, their risk of intracranial bleeding remains problematic and is still somewhat uncertain.
R W Smalling
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  European heart journal     Volume:  18 Suppl F     ISSN:  0195-668X     ISO Abbreviation:  Eur. Heart J.     Publication Date:  1997 Dec 
Date Detail:
Created Date:  1998-03-06     Completed Date:  1998-03-06     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  8006263     Medline TA:  Eur Heart J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  F11-6     Citation Subset:  IM    
Division of Cardiology, University of Texas Medical School at Houston 77030, USA.
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MeSH Terms
Amino Acid Sequence
Fibrinolytic Agents / therapeutic use*
Molecular Sequence Data
Plasminogen Activators / genetics*,  pharmacokinetics,  therapeutic use*
Recombinant Proteins / genetics,  pharmacokinetics,  therapeutic use
Tissue Plasminogen Activator / genetics
Reg. No./Substance:
0/Fibrinolytic Agents; 0/Recombinant Proteins; 133652-38-7/reteplase; EC 3.4.21.-/Plasminogen Activators; EC Plasminogen Activator

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

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