Ex Vivo Inhibition of PAF-Induced β-Thromboglobulin Release in Man by ABT-299, a Potent PAF Antagonist

  • Daniel H. Albert
  • Terrance J. Magoc
  • Hollis D. Kleinert
  • Eugene Sun
  • Ana E. Reyes
  • George W. Carter
  • James B. Summers
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 416)

Abstract

Although still unproved, the therapeutic potential of PAF antagonists for the treatment of diseases with an inflammatory component has been recognized for at least fifteen years. Over this period numerous antagonists encompassing an array of structural classes have been discovered that exhibit moderate to excellent intrinsic potency and are generally effective in animal models of PAF-mediated diseases1,2. However, PAF antagonists for the most part have not proven effective in human disease3–7. To date, the most encouraging results come from the recent report that WEB-2086, when given at higher doses than studied previously to patients with mild to moderate asthma, resulted in improvement in lung function parameters8. In sepsis studies, improvement in survival of a subset of gram-negative patients receiving BN-52021 has also been reported9. A trend toward reduced mortality was also observed in follow-up studies, although the effect did not reach statistical significance10. These modest improvements observed in asthma and the suggestion of a positive effect in sepsis suggest that the currently available antagonists may lack sufficient potency to be optimally effective and support the need for more potent antagonists for human studies.

Keywords

Platelet Activation High Performance Liquid Chro Post Dose Platelet Response High Performance Liquid Chro 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Daniel H. Albert
    • 1
  • Terrance J. Magoc
    • 1
  • Hollis D. Kleinert
    • 1
  • Eugene Sun
    • 1
  • Ana E. Reyes
    • 1
  • George W. Carter
    • 1
  • James B. Summers
    • 1
  1. 1.Abbott LaboratoriesAbbott ParkUSA

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