INHIBITORY EFFECTS OF A NOVEL PAF ANTAGONIST-E6123 ON ANAPHYLACTIC RESPONSES IN PASSIVELY AND ACTIVELY SENSITIZED GUINEA-PIGS AND PASSIVELY SENSITIZED MICE

The effects of the platelet-activating factor (PAF) antagonist, E6123, on anaphylactic responses in guinea pigs and mice were investigated. E6123 inhibited i.v. antigen (Ag)- or inhaled Ag-induced bronchoconstriction in passively and actively sensitized guinea pigs after oral administration at 3 and 10-mu-g/kg, respectively. E6123 inhibited Ag inhalation-induced airway hyperreactivity in guinea pigs after oral administration at 30-mu-g/kg. E6123 protected mice from anaphylactic death with an ED50 value (p.o.) of 7-mu-g/kg. The inhibitory effects of E6123 described above were very potent compared to those of the PAF-antagonists WEB2347 and Y-24180. The present results suggest that E6123 may be beneficial for the treatment of asthma, a condition in which PAF is assumed to be involved.