Reversing Effect of Anti-Asthmatic Drugs on Bronchoconstriction Induced by Antigen Challenge and Histamine in Anesthetized Guinea Pigs.

Abstract

We performed an in vivo evaluation of bronchodilation using a model of antigen-induced bronchoconstriction in anesthetized guinea pigs pretreated with in domethacin, pyrilamine and propranolol, and the results were compared with those for the histamine-induced response. Test drugs were administered intravenously when the antigen or histamine response reached its peak. Leukotriene (LT) D4 antagonists, FPL55712 and LY171883, gradually reduced the antigen-induced response, whereas the lipoxygenase inhibitor phenidone had no such effect. The bronchodilator theophylline rapidly reduced the antigen-induced response, and the adenylate cyclase activator forskolin had a similar effect. The following drugs also had no effect: nifedi pine (calcium-channel antagonist), cromakalim (potassium-channel opener), amlex anox and disodium cromoglycate: DSCG (anti-allergic drugs), OKY-046 (thrombox ane A2 synthetase inhibitor), and dapsone (anti-inflammatory drug). Theophylline, the beta-adrenoceptor agonist salbutamol and the histamine H1-blocker pyrilamine had only a small reversing effect on histamine-induced bronchoconstriction. These re sults suggest that antigen-, but not histamine-, induced bronchoconstriction in anesthe tized guinea pigs is a useful in vivo model for evaluating the bronchodilating effect of anti-asthmatic drugs.Bronchodilators, theophylline and beta adrenoceptor agonists are widely used in the therapy of asthma (1, 2). Theophylline inhibits antigen and agonists-induced bronchospasm in guinea pigs (3, 4), and it also has an anti allergic effect in rats (5, 6). Similarly, beta adrenoceptor agonists, salbutamol and iso proterenol, and the adenylate cyclase activator forskolin have anti-asthmatic and anti-allergic activity (7,8). Calcium-channel antagonists (9, 10) and potassium channel openers (11-13) also exhibit bronchodilating effects in the guinea pig, and anti-allergic drugs, DSCG and amlexanox (14), and the TXA2 synthetase in hibitor OKY-046 (15) inhibit antigen-induced bronchospasm in the guinea pig. However, the bronchodilating effect of these drugs on bron choconstriction in vivo have not been investi gated in detail.The purpose of the present study was to de velop an in vivo system for examining the bronchodilating effect of anti-asthmatic drugs. Therefore, we examined the reversing effects of anti-asthmatic drugs on antigen-induced bronchoconstriction in anesthetized guinea pigs, because antigen causes slowly developing and sustained bronchoconstriction in sensitized guinea pigs pretreated with indomethacin,

Suppressive effects of Y-24180, a receptor antagonist to platelet activating factor (PAF), on antigen-induced asthmatic responses in guinea pigs

“…We therefore investigated the possibility in this study. For this trial, we used the administration timings and doses of the 4 anti-asthmatic drugs according to the previous reports [21,22,24]. The airway hyperresponsiveness is one of the most characteristic features of human asthma [33].…”

“…The first aim of this paper is to describe the effects of Y-24180 on the IAR, LAR, airway hyperresponsiveness, and pulmonary accumulation of eosinophils in actively sensitized guinea pigs that are pretreated additionally with pyrilamine, an anthihistaminic agent. The second aim is to compare thus obtained data with those of several anti-asthmatic drugs such as OKY-046, a thromboxane A 2 (TXA 2 ) synthetase inhibitor [18,19]; ONO-1078, a peptide leukotriene (pLT) receptor antagonist [20,21]; AA-2414, a TXA 2 receptor antagonist [22,23]; and theophylline [24,25].…”