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)
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Authors | L P Feigen, N S Nicholson, L W King, J G Campion, F S Tjoeng, S G Panzer-Knodle |
Journal | The 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 |
PMID | 8263779
(Publication Type: Journal Article)
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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
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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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