title: Inhibitory effects of a novel PAF antagonist E6123 on anaphylactic responses in passively and actively sensitized guinea pigs and passively sensitized mice.
abstract: 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 micrograms/kg, respectively. E6123 inhibited Ag inhalation-induced airway hyperreactivity in guinea pigs after oral administration at 30 micrograms/kg. E6123 protected mice from anaphylactic death with an ED50 value (p.o.) of 7 micrograms/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.
authors.affiliation: Tsukuba Research Lab., Eisai Co., Ltd., Ibaraki, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sakuma
authors.forename: K
authors.initials: K
authors.lastname: Muramoto
authors.forename: K
authors.initials: K
authors.lastname: Harada
authors.forename: S
authors.initials: S
authors.lastname: Katayama
authors.forename: H
authors.initials: H
authors.lastname: Tsunoda
authors.forename: K
authors.initials: K
authors.lastname: Katayama
mesh_terms: D000280:Administration, Inhalation; D000707:Anaphylaxis / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D001249:Asthma / Q000188:drug therapy / Q000276:immunology; D001381:Azepines / Q000627:therapeutic use*; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010047:Ovalbumin / Q000276:immunology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011433:Propranolol / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D000941:Antigens; D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; C068034:WEB 2347; C068035:4-(2-chlorophenyl)-2-(2-(4-isobutylphenyl)ethyl)-6,9-dimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepine; C068033:E 6123; D010047:Ovalbumin; D011433:Propranolol; D011738:Pyrilamine