Studies of the effect of a platelet-activating factor antagonist, CL 184,005, in animal models of gram-negative bacterial sepsis.
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.
Torley
L W
LW
Oncology and Immunology Research Section, Lederle Laboratories, American Cyanamid Company, Pearl River, New York 10965.
Pickett
W C
WC
Carroll
M L
ML
Kohler
C A
CA
Schaub
R E
RE
Wissner
A
A
DeJoy
S Q
SQ
Oronsky
A L
AL
Kerwar
S S
SS
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D007022:Hypotension / Q000503:physiopathology; D015850:Interleukin-6 / Q000096:biosynthesis; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D010539:Permeability; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000633:toxicity; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015850:Interleukin-6; D009943:Organophosphorus Compounds; D010972:Platelet Activating Factor; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; C077460:CL 184005