Antiasthmatic Effect of YM976, a Novel PDE4 Inhibitor, in Guinea Pigs

YM976 is a novel and specific phosphodiesterase 4 inhibitor. In our previous report, we indicated that YM976 has less emeto-genicity, a major adverse effect of PDE4 inhibitors, than rolip-ram. In the present study, we examined the antiasthmatic ef-fects of YM976 in guinea pigs. YM976 orally administered exhibited inhibition of antigen-induced bronchoconstriction, airway plasma leakage, airway eosinophil infiltration, and air-way hyperreactivity (AHR), with ED50 values of 7.3, 5.7, 1.0, and 0.52 mg/kg, respectively. Rolipram also dose dependently sup-pressed these responses. Prednisolone suppressed eosinophil infiltration and AHR, whereas it failed to inhibit bronchocon-striction and plasma leakage. Theophylline moderately sup-pressed bronchoconstriction and edema, but neither eosinophil infiltration nor AHR. YM976 suppressed the peroxidase activit