Pharmacologic modulation of PAF-induced mortality in mice.
The effect of antiinflammatory drugs, phosphodiesterase inhibitors, leukotriene and mediator antagonists and other drug classes were evaluated in a PAF-induced mortality model in mice. By the oral route of administration (-1 hr), dapsone (ED50 = 25 mg/kg), BW 755C (ED50 = 29 mg/kg), theophylline (ED50 = 30 mg/kg) and LY-171,883 (ED50 = 50 mg/kg) protected against PAF-induced lethality in the mouse. Other drugs that afforded protection when given at various dosing schedules and routes were NDGA (100 mg/kg, -18 hr p.o.), diphenyldisulfide (100 mg/kg, -18 hr p.o.), diphenyldisulfide (200 mg/kg, -18 hr p.o.), dexamethasone (1 mg/kg, -3 hr p.o.), dipyridamole (2 mg/kg, -2 min i.v.) and kadsurenone (10 mg/kg, -2 min i.v.). Nonsteroidal antiinflammatory drugs (NSAIDs) such as indomethacin were inactive and the combination of AA-861, a putative 5-LO inhibitor, and indomethacin also failed to prevent PAF-induced lethality. Therefore, our pharmacological data do not consistently support the notion that PAF-induced lethality is due unequivocally to leukotrienes derived from 5-lipoxygenase metabolism.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D005260:Female; D016859:Lipoxygenase Inhibitors; D051379:Mice; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D013189:SRS-A / Q000037:antagonists & inhibitors; D013256:Steroids; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D010726:Phosphodiesterase Inhibitors; D010972:Platelet Activating Factor; D013189:SRS-A; D013256:Steroids; D013930:Thromboxane-A Synthase