Preclinical studies with platelet-activating factor antagonists in models of septic shock

Susan Quinn DeJoy, Arnold L. Oronsky, Michael M. Wick, S. S. Kerwar

Research output: Contribution to journalArticle

Abstract

Since the isolation and elucidation of the structure of platelet-activating factor (PAF) in the late 1970's, several preclinical studies have suggested that PAF is a key mediator of septic shock induced in animals by either endotoxin or by Gram-negative bacteria. A number of PAF antagonists have been sythesized that protect animals from the lethal effects of endotoxin. Some of these antagonists are in early stages of clinical development. The most advanced cadidate is BN 52021, a ginkgolide, that is in Phase II/III clinical trials in patients with septic shock. Preliminary results with BN 52021 indicate that it is efficacious and significantly reduces mortality associated with Gram-negative sepsis. Pivotal trials with BN 52021 aer ongoing. The present review summarizes the biological effects of PAF and the effect of PAF antagonists in animal models of septic shock. The interrelationship of PAF and tumor necrosis factor (another key mediator of septic shock) is also discussed.

Original languageEnglish (US)
Pages (from-to)175-186
Number of pages12
JournalInternational Journal of Antimicrobial Agents
Volume3
Issue number3
DOIs
StatePublished - 1993

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Keywords

  • Combination regimes
  • Platelet-activating factor
  • Platelet-activating factor antagonists
  • Septic shock
  • Therapies for spetic shock
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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