SC-49992, a mimetic of the peptide arginine-glycine-aspartic acid-phenylalanine that blocks platelet aggregation, enhances recombinant tissue plasminogen activator-induced thrombolysis and prevents reocclusion in a canine model of coronary artery thrombosis
| Autor: | L P, Feigen, N S, Nicholson, L W, King, J G, Campion, F S, Tjoeng, S G, Panzer-Knodle |
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| Rok vydání: | 1993 |
| Předmět: |
Male
Bleeding Time Dose-Response Relationship Drug Platelet Aggregation Coronary Thrombosis Molecular Sequence Data Drug Synergism Dipeptides Platelet Membrane Glycoproteins Antibodies Recombinant Proteins Disease Models Animal Dogs Tissue Plasminogen Activator Animals Female Thrombolytic Therapy Amino Acid Sequence Oligopeptides Platelet Aggregation Inhibitors Half-Life |
| Zdroj: | The Journal of pharmacology and experimental therapeutics. 267(3) |
| ISSN: | 0022-3565 |
| Popis: | 8-Guanidino-octanoyl-aspartic acid-phenylalanine (SC-49992), a mimetic of the tetrapeptide arginine-glycine-aspartic acid-phenylalanine, is a potent inhibitor of platelet aggregation. In this study, the authors examined the effects of SC-49992 on the time to lysis of thrombi and the time to reocclusion in the canine coronary artery, which had been treated with tissue plasminogen activator. A lysis/reocclusion model was used that was originally designed so that the reoccluding thrombus was platelet rich. SC-49992 decreased the time to lysis in response to recombinant tissue plasminogen activator in a dose-dependent manner. The reduction of the lytic time was significant at the highest dose of 0.08 mg kg-1 min-1 (from 22.8 +/- 8.2 to 7.4 +/- 1.4 min, P.05). The reocclusion time was prolonged at all doses of SC-49992 (from a control level of 3.4 +/- 0.6 min to more than 50 min at all doses of SC-49992, P.05). At the 0.06- and 0.08-mg kg-1 min-1 doses, all but one animal in each group did not have a reocclusion during the time of the experiment. In those animals that did have reocclusions in the presence of SC-4992, ex vivo platelet aggregation was inhibited 100% at the time of reocclusion. The bleeding times were prolonged in these animals at the levels of inhibition in which the compound was the most effective.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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