Inhibition by Amoxanox (AA-673) of the Immunologically, Leukotriene D&lt;sub&gt;4&lt;/sub&gt;- or Platelet-Activating Factor-Stimulated Bronchoconstriction in Guinea Pigs and Rats

Saijo, Taketoshi; Kuriki, Hisashi; Ashida, Yuzuru; Makino, Haruhiko; Maki, Yoshitaka

doi:10.1159/000233837

Cited by 26 publications

(18 citation statements)

References 25 publications

(32 reference statements)

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“…These results suggest that antigen-induced bronchoconstric tion is already established when it reaches a peak. This interpretation is also supported by our data that the mediator release inhibitor amlexanox, which was prophylactically effec tive and has been reported to exhibit prophyl actic effects on experimental bronchoconstric tion (22), had no reversing effect on antigen induced bronchoconstriction. In the present study, theophylline and the direct adenylate cyclase activator forskolin rapidly reversed the antigen-induced response.…”

Section: Discussionsupporting

confidence: 86%

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

et al. 1992

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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,

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Section: Discussionsupporting

confidence: 86%

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

et al. 1992

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“…Amlexanox clearly inhibited the IL-3-induccd increase in histamine release from leukocytes. Many investigators reported that the antiasthmatic action of amlexanox seems to be related to the inhibition of anti gen-induced mediator release [6][7][8][9][10]. Our present results suggest that another antiallergic mechanism, an anti-IL-3 effect, may contribute to the antiasthmatic action of am lexanox.…”

Section: Discussionsupporting

confidence: 58%

“…The present study was thus undertaken to investi gate the effects of NZ-107 on antigen-, histamine-and LTC4-induced contractions in isolated human bronchial muscle and the effects of NZ-107 on antigen-induced his tamine release from human lung fragments and leuko cytes. Its effects were studied in comparison with those of amlexanox, which has been reported to be an oraly active antiasthmatic drug due to the mast cell-stabilizing activity [6][7][8][9][10], and disodium cromoglycate (DSCG). In some ex periments, salbutamol was used as a reference drug.…”

Section: -Bromo-5-(3-ethoxy-4-mcthoxybcnzylamino)-3(2h)-pyridazinoncmentioning

confidence: 99%

Effect of NZ-107, a Newly Synthesized Pyridazinone Derivative, on Antigen-Induced Contraction of Human Bronchial Strips and Histamine Release from Human Lung Fragments or Leukocytes

Nagai

Suda²,

Iwama³

et al. 1992

Int Arch Allergy Immunol

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The effects of a newly synthesized pyridazinone derivative, NZ-107, 4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone, and two well-known antiasthmatic drugs, amlexanox (orally active disodium cromoglycate-like drug) and disodium cromoglycate (DSCG) on antigen-, histamine- and leukotriene C₄ (LTC₄)-induced constriction of isolated human tracheal muscle, and histamine release from human lung tissues and leukocytes were investigated in vitro. In some experiments, salbutamol was used as a reference drug. NZ-107 inhibited antigen-, histamine- and LTC₄-induced contraction of tracheal muscle. Amlexanox and DSCG did not affect the contractile response of tracheal muscle caused by each stimulant. Salbutamol inhibited antigen-induced contraction of tracheal muscle. NZ-107, amlexanox, DSCG and salbutamol clearly inhibited the antigen-induced release of histamine and LTC₄ from human lung tissue. The antigen-induced histamine release from atopic human leukocytes was inhibited by NZ-107 and amlexanox, but not by DSCG. Pre-treatment with IL-3 did not alter antigen-induced contraction of tracheal muscle and histamine release from lung tissue, but antigen- or calcium ionophore A 23187-induced histamine release from leukocytes was clearly enhanced. Amlexanox inhibited the IL-3-induced enhancement of histamine release from leukocytes in the case of both stimuli, but NZ-107 and DSCG had no effect. These data suggest that NZ-107 has potent anti-allergic actions based on the inhibition of antigen-induced contraction of human tracheal muscle and mediator release from human lung tissue and leukocytes.

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“…It is obvious that tranilast and DSCG inhibit mediator release because both drugs inhibited histamine-release stimulated by the antigen in rat mast cells [19] and monkey and guinea pig lungs [20], Our study suggests that the inhibition of PCA was not due to antagonism to mediators but to inhibi tion of mediator release. On the other hand, antihistaminics such as ketotifen [3,21] and azelastine [4,22,23] which have been reported to inhibit mediator re lease similarly to tranilast and DSCG also inhibited histamine-and serotonin-induced cutaneous reac tions dose dependently. There are many reports [3, 4,; 21, 22] that these drugs have antihistaminic and antiserotonic actions, and the result of our study is in ac cord with the results of such previous studies.…”

Section: Discussionmentioning

confidence: 99%

“…The focus of de velopment of anti-allergic drugs has been to find or ally effective drugs because DSCG is ineffective when given orally. Today, tranilast [2], repirinast [3] and amlexanox [4] are available for clinical use.…”

Section: Introductionmentioning

confidence: 99%

A Method for Evaluating Anti-Allergic Drugs by Simultaneously Induced Passive Cutaneous Anaphylaxis and Mediator Cutaneous Reactions

Koda

Miura

Inagaki

et al. 1990

Int Arch Allergy Immunol

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Homologous passive cutaneous anaphylaxis (PCA) was induced by IgE antibody and, simultaneously, cutaneous reactions were induced by some allergic mediators such as histamine, serotonin and leukotriene (LT) C₄ on rat back skin. Disodium cromoglycate and tranilast with inhibitory actions on mediator release inhibited PCA specifically, whereas antihistaminics, including ketotifen, azelastine, mequitazine and diphenhydramine, inhibited histamine- and serotonin-induced cutaneous reactions as well as PCA. Anti-slow-reacting substance of anaphylaxis drugs, KC-404 and FPL-55712, significantly inhibited PCA and histamine-and serotonin-induced reactions, but at the same doses they did not produce significant inhibition of the LTC₄-induced reaction. All reactions tested were strongly inhibited dose dependently with the β stimulants, salbutamol and isoproterenol, and a xanthine derivative, theophylline, which are known to increase the intra-cellular cyclic AMP level. We think that this method enables the determination of the properties of anti-allergic drugs.

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Inhibition by Amoxanox (AA-673) of the Immunologically, Leukotriene D<sub>4</sub>- or Platelet-Activating Factor-Stimulated Bronchoconstriction in Guinea Pigs and Rats

Cited by 26 publications

References 25 publications

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

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

Effect of NZ-107, a Newly Synthesized Pyridazinone Derivative, on Antigen-Induced Contraction of Human Bronchial Strips and Histamine Release from Human Lung Fragments or Leukocytes

A Method for Evaluating Anti-Allergic Drugs by Simultaneously Induced Passive Cutaneous Anaphylaxis and Mediator Cutaneous Reactions

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