Suppressive effects of F-1322 on the antigen-induced late asthmatic response and pulmonary eosinophilia in guinea pigs.
We investigated the effects of F-1322 (N-[2-[4-(benzhydryloxy)piperidino]ethyl]-3-hydroxy-5-(3-pyridylmethoxy)-2-naphthamide), a new compound that inhibits both thromboxane A2 synthetase and 5-lipoxygenase and that functions as a histamine antagonist, on the Ascaris antigen-induced late asthmatic response and pulmonary eosinophilia in guinea pigs. Oral administration of F-1322 (10-100 mg/kg) inhibited the antigen-induced late asthmatic response in a dose-dependent manner. Histological analysis revealed that F-1322 prevented the accumulation of eosinophils in the airways and this was paralleled by a decrease in the number of eosinophils and lymphocytes recovered in bronchoalveolar lavage fluid. F-1322 (0.1-10 microM) inhibited eotaxin-induced chemotaxis and actin polymerization of eosinophils in vitro in a concentration-dependent manner, while oral administration of F-1322 dose-dependently suppressed the migration of eosinophils into the airways in vivo in response to infusion of interleukin 5 and eotaxin in combination. F-1322 may, thus, improve the late asthmatic response in this model, in part, by preventing the accumulation of eosinophils in the airways. The pharmacological profile of F-1322 indicates that this drug is likely to be useful in the treatment of allergic diseases such as asthma.
Mochizuki
A
A
Pharmaceuticals Research Laboratories, FujiREBIO Inc., 51 Komiya-cho, Tokyo 192-0031, Hachioji, Japan. aki.mochizuki@nifty.com
Tamura
N
N
Yatabe
Y
Y
Onodera
S
S
Hiruma
T
T
Inaba
N
N
Kusunoki
J
J
Tomioka
H
H
D000403:Airway Resistance / Q000187:drug effects; D000485:Allergens; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D000947:Antigens, Helminth; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000008:administration & dosage; D002633:Chemotaxis; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology*; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D006168:Guinea Pigs; D015848:Interleukin-5 / Q000008:administration & dosage; D008171:Lung Diseases / Q000276:immunology*; D009281:Naphthalenes / Q000494:pharmacology*; D013997:Time Factors
D000485:Allergens; D018927:Anti-Asthmatic Agents; D000947:Antigens, Helminth; D054413:Chemokine CCL11; D019742:Chemokines, CC; C096516:F 1322; D015848:Interleukin-5; D009281:Naphthalenes