Comparative Pharmacology of Site Directed Antithrombin Agents. Implication in Drug Development
| Autor: | Jawad Fareed, Demetra Callas |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Plasmin
Lipoproteins Molecular Sequence Data Polynucleotides Drug Evaluation Preclinical Oligonucleotides Hemorrhage Pharmacology Antithrombins Structure-Activity Relationship Thrombin Tissue factor pathway inhibitor Hirudin Therapy medicine Animals Humans Protease Inhibitors Amino Acid Sequence Urokinase Clinical Trials as Topic business.industry Fibrinolysis Antithrombin Hematology Heparin Aptamers Nucleotide Hirudins Peptide Fragments Recombinant Proteins Drug development Drug Design Rabbits business Forecasting medicine.drug Discovery and development of direct thrombin inhibitors |
| Zdroj: | Thrombosis and Haemostasis. 74:473-481 |
| ISSN: | 2567-689X 0340-6245 |
| DOI: | 10.1055/s-0038-1642724 |
| Popis: | Beside the direct inhibition of thrombin and its regulatory functions, many of the newer antithrombin agents produce several additional effects, unrelated to their anticoagulant actions. Synthetic peptide inhibitors are capable of producing fibrinolytic compromise by virtue of their actions on fibrinolytic enzymes such as t-PA, plasmin, urokinase and protein Ca. In addition, the low molecular weight arginine-containing peptides are also known to produce hemodynamic and hemostatic deficits. The designs of the ongoing clinical trials are largely empirical because of the non-availability of valid pharmacologic and toxicologic data on thrombin inhibitors. In contrast to heparin, none of the thrombin inhibitors produce endogenous release of tissue factor pathway inhibitor (TFPI) in the experimental and clinical settings. These observations suggest that beside the direct inhibition of thrombin, these agents also produce multiple additional effects that can significantly contribute to their pharmacologic and toxicologic profile. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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