Abstract |
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.
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Authors | A Mochizuki, N Tamura, Y Yatabe, S Onodera, T Hiruma, N Inaba, J Kusunoki, H Tomioka |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 430
Issue 1
Pg. 123-33
(Oct 26 2001)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 11698072
(Publication Type: Journal Article)
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Chemical References |
- Allergens
- Anti-Asthmatic Agents
- Antigens, Helminth
- Chemokine CCL11
- Chemokines, CC
- F 1322
- Interleukin-5
- Naphthalenes
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Topics |
- Airway Resistance
(drug effects)
- Allergens
- Animals
- Anti-Asthmatic Agents
(pharmacology)
- Antigens, Helminth
- Asthma
(drug therapy, etiology, immunology)
- Bronchoalveolar Lavage Fluid
(cytology)
- Cell Movement
(drug effects)
- Cells, Cultured
- Chemokine CCL11
- Chemokines, CC
(administration & dosage)
- Chemotaxis
- Disease Models, Animal
- Eosinophilia
(immunology)
- Eosinophils
(drug effects, immunology)
- Guinea Pigs
- Interleukin-5
(administration & dosage)
- Lung Diseases
(immunology)
- Naphthalenes
(pharmacology)
- Time Factors
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