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.