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Published on: June 29, 2015
Effect of platelet activating factor antagonists in different models of thrombosis
1Pharmacology Division, Central Drug Research Institute, Lucknow, India.
Abstract:
Effect of three specific PAF antagonists, SR-27417, BN-50739 and ginkgolide derivative BN-52021 have been evaluated in models of thrombosis in the mouse, rat and cat. Thrombosis in the mouse was induced by intravenous infusion of collagen and adrenaline. In rats it was induced by inserting a metallic wire into the inferior vena cava. In the cat, thrombus formation was assessed in the extracorporeal shunt. All the antagonists offered a dose-dependent protection against pulmonary thromboembolism in mice (1, 3 and 10 mg/kg) and the thrombosis monitored in the extracorporeal shunt in cats (0.3, 1 and 3 mg/kg). In rats, no significant protection was observed with these antagonists even at the highest dose used.
Insights
Three platelet-activating factor (PAF) antagonists showed dose-dependent protection against thrombosis in mice and cats. However, these PAF antagonists were ineffective in preventing thrombosis in rats, indicating species-specific effects.
Area of Science:
- Pharmacology
- Thrombosis Research
- Cardiovascular Science
Background:
- Platelet-activating factor (PAF) is a potent lipid mediator involved in inflammation and thrombosis.
- PAF antagonists are investigated for their potential to prevent thrombotic events.
Purpose of the Study:
- To evaluate the efficacy of three PAF antagonists (SR-27417, BN-50739, and BN-52021) in preclinical models of thrombosis.
- To assess potential species-specific differences in the effectiveness of these antagonists.
Main Methods:
- Thrombosis was induced in mice via collagen and adrenaline infusion.
- Rat models involved thrombosis induction by metallic wire insertion into the inferior vena cava.
- Cat models assessed thrombus formation in an extracorporeal shunt.
Main Results:
- PAF antagonists demonstrated dose-dependent protection against pulmonary thromboembolism in mice.
- Effective protection against thrombosis was observed in cats using the extracorporeal shunt model.
- No significant antithrombotic effect was observed in rats, even at the highest doses tested.
Conclusions:
- PAF antagonists exhibit varying efficacy across different species.
- SR-27417, BN-50739, and BN-52021 show promise in managing thrombosis in mice and cats.
- Further research is needed to understand the lack of efficacy in rats and potential clinical applications.
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