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Preclinical evaluation of S18886 in an experimental model of coronary arterial thrombosis
- Source :
- Journal of cardiovascular pharmacology. 48(5)
- Publication Year :
- 2006
-
Abstract
- The specific thromboxane receptor antagonist, S18886, was evaluated for prevention of coronary arterial thrombosis and myocardial ischemia-reperfusion in anesthetized canines. For the primary thrombosis study in left circumflex (LCX) coronary artery, 26 dogs were randomized to receive either vehicle (n = 7) or intravenous S18886 (0.3 mg/kg, n = 6; 1.0 mg/kg, n = 6; and 3.0 mg/kg, n = 7). The respective times to occlusion after S18886 were as follows: 56.8 +/- 9.3, 83.5 +/- 14.9, and 92.4 +/- 15.7 minutes compared to 43.3 +/- 8.2 minutes after vehicle. S18886 caused a minimal increase in tongue bleeding time and a significant decrease in ex vivo platelet aggregation to arachidonic acid or U46619. Another 37 dogs were randomized to receive placebo (n = 12), clopidogrel 1.0 mg/kg p.o. QDX3 (n = 9), clopidogrel + S18886 0.3 (n = 9) or 1.0 (n = 7) mg/kg intravenous. Clopidogrel produced a 50% reduction in adenosine diphosphate-induced platelet aggregation and a slight increase in the time to occlusion. However, clopidogrel + S18886 1.0 mg/kg prevented occlusive thrombus formation in most of the coronary vessels over 6 hours. S18886 did not alter myocardial infarct size in the ischemia-reperfusion model. In conclusion, S18886 alone caused a dose-dependent prolongation in the time to primary occlusive coronary artery thrombosis, whereas S18886 + clopidogrel displayed effective in preventing occlusive thrombus formation with only a moderate increase of tongue-bleeding time.
- Subjects :
- medicine.medical_specialty
Platelet Aggregation
Receptors, Thromboxane
Drug Evaluation, Preclinical
Naphthalenes
Placebo
Dogs
Internal medicine
Occlusion
medicine
Animals
Platelet
cardiovascular diseases
Myocardial infarction
Carotid Artery Thrombosis
Pharmacology
business.industry
Clopidogrel
medicine.disease
Thrombosis
Disease Models, Animal
medicine.anatomical_structure
Terutroban
Anesthesia
Cardiology
Propionates
Cardiology and Cardiovascular Medicine
business
medicine.drug
Artery
Subjects
Details
- ISSN :
- 01602446
- Volume :
- 48
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Journal of cardiovascular pharmacology
- Accession number :
- edsair.doi.dedup.....492ab513c8aff33b17860ca39ae363b3