Anti-inflammatory and bronchodilator properties of KF19514, a phosphodiesterase 4 and 1 inhibitor.

Abstract We investigated the effects of KF19514 (5-phenyl-3-(3-pyridyl)methyl-3H-imidazo[4,5- c ][1,8]naphthyridin-4(5H)-one) on bronchoconstriction and allergic inflammation in guinea pigs and on tumor necrosis factor-α production in mice. KF19514 inhibited phosphodiesterase 4 (IC 50 =0.40 μM) and phosphodiesterase 1 (IC 50 =0.27 μM) derived from canine tracheal smooth muscles. KF19514 relaxed contracted tracheal smooth muscle and had a potent inhibitory effect on antigen-induced bronchoconstriction (EC 50 =0.058 μM) in vitro. Intravenous administration of KF19514 inhibited histamine-induced bronchoconstriction (ID 50 =2.8 μg/kg i.v.). Moreover, oral administration of KF19514 inhibited anaphylactic bronchoconstriction (ID 50 =0.2 mg/kg p.o.), and eosinophil infiltration in airway stimulated with platelet-activating factor (PAF) or antigen. KF19514 also produced a significant inhibition of tumor necrosis factor-α production in mice (ID 50 =0.023 mg/kg p.o.). Finally, KF19514 completely inhibited antigen-induced hyperreactivity at 0.1 mg/kg p.o. These results demonstrate that KF19514 may have efficacy in the treatment of asthma.