title: [Effect of KW-4679, a novel antiallergic drug, on platelet-activating factor (PAF)-induced bronchoconstriction, airway hyperresponsiveness and pulmonary cell accumulation in guinea pigs].
abstract: We assessed the effects of KW-4679 on bronchoconstriction, airway hyperresponsiveness and infiltration of inflammatory cells into the bronchoalveolar lavage (BAL) fluid induced by platelet-activating factor (PAF) in guinea pigs. (1) KW-4679 (1, 10 mg/kg, p.o.) significantly inhibited PAF-induced bronchoconstriction in anesthetized, ventilated guinea pigs. Ketotifen (1, 10 mg/kg, p.o.) also significantly inhibited that reaction. (2) Intravenous administration of PAF (600 ng/kg/hr) to ventilated anesthetized guinea pigs induced bronchial hyperresponsiveness to histamine or substance P. PAF-induced bronchial hyperresponsiveness was significantly attenuated by pretreatment with KW-4679 (3 mg/kg, i.v.). (3) Exposure of guinea pigs to an aerosol of PAF induced an increase in the numbers of total leukocytes, eosinophils, neutrophils and lymphocytes in BAL fluid at 24 hr. KW-4679 (10 mg/kg, p.o.) reduced the increase in eosinophils in BAL fluid. Ketotifen (10 mg/kg, p.o.) partially reduced the increase in eosinophils in BAL fluid. (4) KW-4679 did not inhibit PAF-induced rabbit platelet aggregation. These observations indicate that KW-4679 attenuates the PAF-induced pulmonary reactions in guinea pigs and that these actions may be beneficial for the treatment of allergic bronchial asthma.
authors.affiliation: Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: T
authors.initials: T
authors.lastname: Ikemura
authors.forename: H
authors.initials: H
authors.lastname: Ishii
authors.forename: S
authors.initials: S
authors.lastname: Kitamura
authors.forename: K
authors.initials: K
authors.lastname: Ohmori
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016084:Bronchoconstriction / Q000187:drug effects*; D003990:Dibenzoxepins / Q000494:pharmacology* / Q000627:therapeutic use; D006168:Guinea Pigs; D007665:Ketotifen / Q000494:pharmacology / Q000627:therapeutic use; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D000069605:Olopatadine Hydrochloride; D010972:Platelet Activating Factor; D011817:Rabbits
chemical_list: D018926:Anti-Allergic Agents; D003990:Dibenzoxepins; D010972:Platelet Activating Factor; D000069605:Olopatadine Hydrochloride; D007665:Ketotifen