Effect of NZ-107 on late-phase airway responses and airway hyperreactivity in guinea pigs

The effect of NZ-107 (4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone) on late-phase airway responses and airway hyperreactivity was investigated in the guinea pig. Challenge with inhaled ovalbumin in conscious guinea pigs actively sensitized with inhaled ovalbumin caused triphasic bronchial obstruction, which peaked at 5-30 min, 6-8 h and 24 h. In this model, airway hyperreactivity to acetylcholine was observed 48 h after antigen challenge. Orally administered NZ-107, given 2 h before ovalbumin challenge significantly inhibited airway responses at 5-30 min (10 mg/kg), 6-8 h (30 mg/kg), 24 h (10 mg/kg) and airway hyperreactivity (30 mg/kg). When NZ-107 (10 mg/kg) was orally administered to the guinea pigs 3 h after ovalbumin challenge, it also inhibited airway responses at 6-8 h and 24 h and airway hyperreactivity. In anaesthetized guinea pigs, intravenous administration of NZ-107 (0.03-1.0 mg/kg) inhibited platelet-activating factor (PAF)- and propranolol-induced airway hyperreactivity to histamine. These results suggest that NZ-107 may be a useful drug for the treatment of bronchial asthma by reducing late-phase airway responses and airway hyperreactivity.