Effect of a peptide leukotriene receptor antagonist, ONO-1078, on guinea-pig models of asthma.
Peptide leukotrienes have been suggested to play an important role in bronchial asthma. As antigen-induced bronchoconstrictions, airway hyperreactivity, and pulmonary eosinophil accumulation are characteristics of the pathology of asthma, we investigated the effect of a peptide leukotriene receptor antagonist, ONO-1078, on these responses using guinea-pig models of asthma. Oral administration of ONO-1078 (3 mg/kg) significantly inhibited slow-reacting substance of anaphylaxis-mediated bronchoconstriction induced by i.v. administered ovalbumin. ONO-1078 (30-100 mg/kg), when administered orally both 1 h before and 4 h after ovalbumin challenge, significantly reduced immediate- and late-phase asthmatic responses, with peak responses occurring immediately and 5-11 h after challenge with inhaled ovalbumin. Oral administration of ONO-1078 significantly reduced the airway hyperreactivity (10-30 mg/kg) and the pulmonary eosinophil accumulation (30-100 mg/kg) observed 4 and 24 h after ovalbumin challenge, respectively. These results suggest that ONO-1078 may be of therapeutic use for bronchial asthma.
Minåse Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
N
N
Nakagawa
T
T
Obata
T
T
Kobayashi
Y
Y
Okada
F
F
Nambu
T
T
Terawaki
T
T
Furuya
K
K
Muryobayashi
M
M
Sawada
H
H
Aishita
D000109:Acetylcholine / Q000502:physiology; D000210:Acute-Phase Reaction / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects* / Q000276:immunology; D001993:Bronchodilator Agents / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology*; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D007114:Immunization; D008297:Male; D010047:Ovalbumin / Q000494:pharmacology; D010793:Phthalazines / Q000494:pharmacology; D011657:Pulmonary Eosinophilia / Q000188:drug therapy; D011738:Pyrilamine / Q000494:pharmacology; D013189:SRS-A / Q000037:antagonists & inhibitors*
D001993:Bronchodilator Agents; D002867:Chromones; D010793:Phthalazines; D013189:SRS-A; C006312:FPL 55712; D010047:Ovalbumin; D011738:Pyrilamine; D000109:Acetylcholine; C047681:pranlukast; C020976:azelastine