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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.

Abstract
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)
AuthorsL P Feigen, N S Nicholson, L W King, J G Campion, F S Tjoeng, S G Panzer-Knodle
JournalThe Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 267 Issue 3 Pg. 1191-7 (Dec 1993) ISSN: 0022-3565 [Print] United States
PMID8263779 (Publication Type: Journal Article)
Chemical References
  • 8-guanidino-octanoyl-Asp-Phe
  • Antibodies
  • Dipeptides
  • Oligopeptides
  • Platelet Aggregation Inhibitors
  • Platelet Membrane Glycoproteins
  • Recombinant Proteins
  • arginyl-glycyl-aspartyl-phenylalanine
  • Tissue Plasminogen Activator
Topics
  • Amino Acid Sequence
  • Animals
  • Antibodies (pharmacology)
  • Bleeding Time
  • Coronary Thrombosis (prevention & control)
  • Dipeptides (pharmacokinetics, therapeutic use)
  • Disease Models, Animal
  • Dogs
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Female
  • Half-Life
  • Male
  • Molecular Sequence Data
  • Oligopeptides (pharmacology)
  • Platelet Aggregation (drug effects)
  • Platelet Aggregation Inhibitors (pharmacokinetics, therapeutic use)
  • Platelet Membrane Glycoproteins (immunology)
  • Recombinant Proteins (therapeutic use)
  • Thrombolytic Therapy
  • Tissue Plasminogen Activator (therapeutic use)

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