The inhibitory effect of TMK688, a novel anti-allergic drug having both 5-lipoxygenase inhibitory activity and anti-histamine activity, against bronchoconstriction, leukotriene production and inflammatory cell infiltration in sensitized guinea pigs
| Autor: | Toshiharu Kamitani, S. Nakajima, T. Shizawa, Yuji Tohda, S. Ohmori, H. Satoh, Kazuha Maeda, T. Ishii |
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| Rok vydání: | 1997 |
| Předmět: |
Ketotifen
medicine.medical_specialty Leukotriene medicine.medical_treatment Immunology Leukotriene Production Azelastine chemistry.chemical_compound Endocrinology chemistry Internal medicine medicine Immunology and Allergy Antihistamine Bronchoconstriction Oxatomide medicine.symptom Histamine medicine.drug |
| Zdroj: | Clinical & Experimental Allergy. 27:110-118 |
| ISSN: | 0954-7894 |
| DOI: | 10.1111/j.1365-2222.1997.tb00680.x |
| Popis: | Summary Background TMK688 is being developed as ati anti-allergic drug having both 5-lipoxygenasc inhibitory activity atid anti-histaminc activity. Method We compared the inhibition ol the late asthmatic rcsponses by TMK688 with that by other anti-allergic agents in actively sensitized guinea pigs, and examined the relationship between 5-lipoxygetiase inhibition and the late asthmatic responses Results At 1–3.2 mg/kg, TMK688 inhibited the increases in respiratory resistance, leukotriene (LT) B4 and C4 production in the lungs and eosinophil infiltralion into the alveoli during the late asthmatic response, whereas the eliects tended to lessen at the dose of 10mg/kg. These effects are thought to be caused by the 5-lipoxygenase inhibitory activity of TMK688 because Azelastine. an anti-allergic drug having potent antihistamine activity, exhibited no effect. ONO-1078. a peptide LT antagonist. inhibited the late-phase bronchoconstriction at a dose of 100mg/kg p.o., but not the increase in the infiltration of inflammatory cells into the alveoli, suggesting that the late-phase bronchoconstriction is induced, in part, by peptide LTs, i.e. LT C4, D4 and E4 atid that the inflammatory cell infiltration may be caused by LTB4, TMK688 inhibited the immediate bronchoconstriction dose-dependently, and the effect was significant at a dose of 10mg/kg orally. Since Azelastine, Ketotifen and Oxatomide suppressed the bronchoconstriction at far lower doses than did TMK688, the inhibitory effect was mainly caused by its antihistamine activity. Conclusions TMK688 appears to be a novel anti-allergic drug having inhibitory effects on both the bronchoconstriction and the infiltration of inflatnmutory cells during late asthmatic responses. |
| Databáze: | OpenAIRE |
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