Activity of a novel thienodiazepine derivative as a platelet-activating factor antagonist in guinea pig lungs. Effects on platelet-activating factor and allergen induced eosinophil accumulation.
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| Abstract |
Platelet-activating factor (PAF) inhalation in guinea pigs caused a significant increase in the number of eosinophils recovered from bronchoalveolar lavage fluid (BALF). Oral administration of (S)-(+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11- dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f] [1,2,4]triazolo[4,3-a][1,4]diazepine (E-6123), a novel PAF antagonist, at the dose of 100 micrograms/kg completely inhibited the PAF-induced eosinophil accumulation. Antigen inhalation in passively sensitized guinea pigs caused a significant increase in lung contents of PAF at 5 min, and accumulation of eosinophils in the bronchi 1 and 2 days thereafter, E-6123 inhibited the antigen-induced eosinophil accumulation and the maximum inhibition was approximately 65%. On the other hand, methylprednisolone completely inhibited the antigen-induced eosinophil accumulation. The results suggest that PAF is a potent attractant of eosinophils and is involved in antigen-induced eosinophil infiltration into bronchi. The results also suggest that E-6123 may be of therapeutic value in the treatment of asthma exhibiting eosinophil recruitment in airways.
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| Authors | H Tsunoda, Y Sakuma, M Shirato, H Obaishi, K Harada, K Yamada, N Shimomura, Y Machida, I Yamatsu, K Katayama |
| Journal | Arzneimittel-Forschung (Arzneimittelforschung) Vol. 41 Issue 3 Pg. 224-7 (Mar 1991) ISSN: 0004-4172 [Print] Germany |
| PMID | 1867658 (Publication Type: Journal Article) |
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