Effect of platelet activating factor antagonists in different models of thrombosis

P Seth1, R Kumari, M Dikshit

  • 1Pharmacology Division, Central Drug Research Institute, Lucknow, India.

Thrombosis Research
|December 15, 1994
PubMed

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.

Related Concept Videos

Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Formation of the Platelet Plug01:22

Formation of the Platelet Plug

The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...