Studies of the effect of a platelet-activating factor antagonist, CL 184,005, in animal models of gram-negative bacterial sepsis

L. W. Torley, W. C. Pickett, M. L. Carroll, C. A. Kohler, R. E. Schaub, A. Wissner, S. Q. DeJoy, A. L. Oronsky, S. S. Kerwar

Research output: Contribution to journalArticle

Abstract

The effect of CL 184,005, a potent and specific platelet-activating factor antagonist, has been examined in a variety of animal models relevant to gram- negative bacterial sepsis. Pretreatment of mice with CL 184,005 protected them from the lethal effects of platelet-activating factor. When rats or primates rendered hypotensive with endotoxin were treated with CL 184,005, blood pressure was normalized. Pretreatment of rats with CL 184,005 protected them from the gastrointestinal lesions induced by endotoxin. Pretreatment of rats and mice with CL 184,005 protected them from the lethal effects of endotoxin. Plasma tumor necrosis factor levels in endotoxin-treated mice were lower when the mice were pretreated with CL 184,005. These observations suggest that CL 184,005 may be potentially useful in the treatment of gram- negative bacterial sepsis, and the agent is undergoing clinical evaluation.

Original languageEnglish (US)
Pages (from-to)1971-1977
Number of pages7
JournalAntimicrobial agents and chemotherapy
Volume36
Issue number9
DOIs
StatePublished - Jan 1 1992

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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    Torley, L. W., Pickett, W. C., Carroll, M. L., Kohler, C. A., Schaub, R. E., Wissner, A., DeJoy, S. Q., Oronsky, A. L., & Kerwar, S. S. (1992). Studies of the effect of a platelet-activating factor antagonist, CL 184,005, in animal models of gram-negative bacterial sepsis. Antimicrobial agents and chemotherapy, 36(9), 1971-1977. https://doi.org/10.1128/AAC.36.9.1971