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We employed an ex vivo [(3)H]rolipram binding experiment to elucidate the mechanism of emetic activity of phosphodiesterase 4 inhibitors. In Suncus murinus (an insectivore used for evaluation of emesis), emetic potential as well as ability to occupy the high-affinity rolipram binding site in brain membrane fraction in vivo were determined for(More)
We examined in this study the effect of KF19514, a phosphodiesterase 4 and 1 inhibitor, on antigen-induced lung inflammation by inhaled administration in guinea-pigs. It was previously reported that inhaled KF19514 prevented antigen-induced bronchoconstriction and platelet-activating factor (PAF)-induced lung inflammation. In fact, a variety of factors(More)
Phosphodiesterase (PDE) 4 inhibitors are well known for their inhibitory effect on bronchoconstriction and inflammation and may be promising anti-asthma drugs. Platelet-activating factor (PAF) has been proposed as an inflammatory mediator to be relevant to asthma. It causes bronchoconstriction, airway microvascular leakage, inflammatory cell accumulation in(More)
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-alpha production in mice. KF19514 inhibited phosphodiesterase 4 (IC50 = 0.40 microM) and phosphodiesterase 1 (IC50 = 0.27 microM) derived from canine(More)
Objective: We examined the effect of erdosteine (KW-9144), an expectorant, and related compounds on inflammatory cell-derived reactive oxygen species which are involved in airway inflammation.¶Methods: Neutrophils were isolated from peritoneal lavages of casein-injected rats and from peripheral blood of healthy human donors. Eosinophils were isolated from(More)
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