title: Bronchoprotective effects of KF-19514 and cilostazol in guinea pigs in vivo.
abstract: It has been shown that inhibitors of cyclic nucleotide phosphodiesterase III and IV have a bronchodilator effect. We compared the effects of a selective phosphodiesterase III inhibitor, 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-quin olinone (cilostazol) and a phosphodiesterase I/IV inhibitor, 5-phenyl-3-(3-pyridil) methyl-3H-imidazo[4,5-c][1,8]naphthyridin-4(5H)-one (KF-19514) on antigen- and histamine-induced bronchoconstriction in guinea pigs in vivo. Intravenous administration of cilostazol and KF-19514 inhibited histamine- and antigen-induced bronchoconstriction in a dose-dependent manner. When assessing the resulting ED50 values, the activity of KF-19514 against antigen-induced bronchoconstriction was stronger than its antagonism of histamine-induced bronchoconstriction (0.004 vs. 0.056 mg/kg). while those of cilostazol were contrary (0.835 vs. 0.031 mg/kg). These results suggest that although both inhibitors of phosphodiesterase III and phosphodiesterase IV have a bronchodilator or bronchoprotective effect, phosphodiesterase IV inhibitors such as KF-19514 may be more useful for asthma treatment because KF-19514 had an anti-allergic effect in addition to the functional bronchodilator activity.
authors.affiliation: The Third Department of Internal Medicine, Kanazawa University School of Medicine, Takara-machi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Fujimura
authors.forename: T
authors.initials: T
authors.lastname: Kita
authors.forename: S
authors.initials: S
authors.lastname: Myou
authors.forename: H
authors.initials: H
authors.lastname: Tachibana
authors.forename: T
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D000077407:Cilostazol; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008297:Male; D009287:Naphthyridines / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology*; D013806:Theophylline / Q000494:pharmacology
chemical_list: D001993:Bronchodilator Agents; C106878:KF 19514; D009287:Naphthyridines; D010726:Phosphodiesterase Inhibitors; D013777:Tetrazoles; D006632:Histamine; D013806:Theophylline; D000077407:Cilostazol