Antiplatelet and antithrombotic activity of SL65.0472, a mixed 5-HT1B/5-HT2A receptor antagonist
| Autor: | Monique Delahaye, Andre Bernat, Paul J. Schaeffer, Philippe Janiak, Sylvette Lochot, Irène Lechaire, Patrice Ferrari, Jean-Marc Herbert, Alain Grosset, Stephen E. O'Connor, Pierre Savi, Janine Lorrain, Nicole Duval, Christopher N. Berry, Alain Lalé |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
medicine.medical_specialty Pathology medicine.drug_class Piperazines Arteriovenous Shunt Surgical Dogs Fibrinolytic Agents Internal medicine Antithrombotic medicine Animals Humans Platelet Receptor Serotonin 5-HT2A Platelet activation Thrombus Dose-Response Relationship Drug business.industry Rats Inbred Strains Thrombosis Hematology medicine.disease Receptor antagonist Platelet Activation Rats Dose–response relationship Disease Models Animal Endocrinology Receptors Serotonin Quinolines Receptor Serotonin 5-HT1B Platelet aggregation inhibitor Female Rabbits Serotonin Antagonists business Fibrinolytic agent Platelet Aggregation Inhibitors |
| Zdroj: | Europe PubMed Central |
| ISSN: | 0340-6245 |
| Popis: | SummaryThe antiplatelet and antithrombotic activity of SL65.0472 (7-fluoro-2-oxo-4-[2-[4-(thieno [3,2-c]pyrin-4-yl) piperazin-1-yl]ethyl]-1,2-dihydroquinoline-acetamide), a mixed 5-HT1B/5-HT2A receptor antagonist was investigated on 5HT-induced human platelet activation in vitro, and in rat, rabbit and canine platelet dependent thrombosis models. SL65.0472 inhibited 5-HT-induced platelet shape change in the presence of EDTA (IC50 values = 35, 69 and 225 nM in rabbit, rat and human platelet rich plasma (PRP)), and also inhibited aggregation induced in human PRP by 3-5 μM 5-HT + threshold concentrations of ADP (0.5-1 M) or collagen (0.3 g/ml) with mean IC50 values of 49 ± 13 and 48 ± 6 nM respectively. SL65.0472 inhibited thrombus formation when given both intravenously 5 min and orally 2 h prior to assembly of an arterio-venous (A-V) shunt in rats as from 0.1 and 0.3 mg/kg respectively. It was active in a rabbit A-V shunt model with significant decreases in thrombus weight as from 0.1 mg/kg i. v. and at 10 mg/kg p. o. The delay to occlusion in an electric current-induced rabbit femoral artery thrombosis model was increased by 251% (p |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|