Academic Journal
Leukotriene Receptor Antagonism and Augmentation of β-Receptor-mediated Events by LY171883
| العنوان: | Leukotriene Receptor Antagonism and Augmentation of β-Receptor-mediated Events by LY171883 |
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| المؤلفون: | Rinkema, Lynn E, Roman, Carlos R, Russell, Weihua L, Spaethe, Stephen M, Bemis, Kerry G, Henry, David P, Marshall, Winston S, Fleisch, Jerome H |
| المصدر: | Journal of Pharmacy and Pharmacology ; volume 42, issue 9, page 620-625 ; ISSN 2042-7158 0022-3573 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 1990 |
| مصطلحات موضوعية: | Pharmaceutical Science, Pharmacology |
| الوصف: | LY171883, (1-[2-hydroxy-3-propyl-4-((4(1H-tetrazol-5-yl)butoxy)phenyl]ethanone), a leukotriene (LT) D4/E4 receptor antagonist, was assessed in comparison with two well known phosphodiesterase inhibitors, isobutylmethyl-xanthine (IBMX) and theophylline, for its ability to augment β-receptormediated responses. Relaxation of carbachol-contracted guinea-pig trachea by isoprenaline was enhanced by the three agents in a dose-dependent manner. A two-fold enhancement of isoprenaline-induced smooth muscle relaxation was produced by 2.5 μM IBMX, 28 μM LY171883, or 140 μM theophylline. Similar concentrations of IBMX or theophylline did not antagonize LTE4-induced tracheal contractions; LY171883 totally inhibited the response and had significant LTE4 receptor antagonist activity even at 10-fold lower concentrations. Antigen-induced release of histamine and LTC4 from guinea-pig lung was reduced by isoprenaline. Prior treatment with LY171883, IBMX, or theophylline did not enhance this action. Isoprenaline reduced histamine-induced bronchospasm in anaesthetized guinea-pigs. LY171883, 30 mg kg−1, or IBMX, 1 mg kg−1, did not affect the isoprenaline-induced decrease in the histamine response. IBMX, 3 mg kg−1, and theophylline, 30 mg kg−1, augmented the isoprenaline-induced bronchodilation. LTE4-induced bronchoconstriction was not affected by IBMX or theophylline whereas LY171883 antagonized this response at doses as low as 3 mg kg−1. Therefore, in both in-vitro and in-vivo test systems, LY171883 functioned primarily as a leukotriene receptor antagonist with minimal pharmacological activity attributable to its ability to potentiate isoprenaline. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1111/j.2042-7158.1990.tb06619.x |
| الاتاحة: | http://dx.doi.org/10.1111/j.2042-7158.1990.tb06619.x https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.2042-7158.1990.tb06619.x http://academic.oup.com/jpp/article-pdf/42/9/620/37238455/j.2042-7158.1990.tb06619.x.pdf |
| Rights: | https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model |
| رقم الانضمام: | edsbas.A27D115B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/j.2042-7158.1990.tb06619.x |
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