Inhibitors of the Release of Anaphylactic Mediators

Garland, L.G.; Green, A. F.; Hodson, H. F.

doi:10.1007/978-3-642-66891-3_16

Cited by 4 publications

(5 citation statements)

References 166 publications

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“…Structure-activity relationships for the chromone-2-carboxylic acids and related compounds, as judged by the inhibition of the rat PCA reaction, have been reviewed by GARLAND et al [18]. Some of the molecular features required for activity in this model have been outlined but clearly the properties conferring activity in other test systems, or resulting in a broad-spectrum of activity, remain to be elucidated.…”

Section: Discussionmentioning

confidence: 98%

“…The compound strongly inhibited histamine secretion from the rat cells, was less active against the hamster and totally ineffective against the mouse. In fact, the drug shows a high degree of selectivity in its action and, as judged by direct and indirect criteria, appears to be essentially ineffective against cutaneous mast cells of the mouse, guinea-pig, primates, rabbit and cow, human basophil leucocytes, intestinal mast cells of the rat, and pulmonary mast cells of the guinea-pig, cow or dog (for reviews see [2,18,19]). The compound is also surprisingly weakly active against mast cells from human lung [17,20], thereby providing an interesting contrast to its clinical efficacy in human bronchial asthma.…”

Section: Discussionmentioning

confidence: 99%

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Differential effects of anti-allergic compounds on peritoneal mast cells of the rat, mouse and hamster

1984

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The effects of various inhibitors and anti-allergic drugs on histamine secretion from peritoneal mast cells of the rat, mouse and hamster have been compared. Phosphodiesterase inhibitors, cAMP analogues and beta-adrenoceptor agonists variously blocked release of the amine from all three cell types. The mouse cells were rather less sensitive to the former agents than those of the rat and hamster. Disodium cromoglycate inhibited histamine secretion from rat peritoneal mast cells, was less active against the hamster cells and completely ineffective against those of the mouse. Other chromones showed varied patterns of differential reactivity but phloretin and the flavonoid quercetin were essentially equiactive against all three cell types. The tetrazoles AH 9679 and doxantrazole prevented histamine release in each case but were significantly less active against the mouse cells. These results further emphasize the functional heterogeneity of mast cells from different sources.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Differential effects of anti-allergic compounds on peritoneal mast cells of the rat, mouse and hamster

1984

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“…We found that topically applied histamine had no effect on edema while significantly suppressing MPO accumulation. Antihistamines can exhibit either antagonist or agonist effects depending on dose [13], and are thus theoretically capable of either potentiating or suppressing the ability of endogenous histamine to inhibit myeloperoxidase accumulation. It is noteworthy that of all the compounds tested only corticosteroids were potent inhibitors of both edema and MPO accumulation.…”

Section: Discussionmentioning

confidence: 99%

Edema and cell infiltration in the phorbol ester-treated mouse ear are temporally separate and can be differentially modulated by pharmacologic agents

et al. 1989

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The temporal patterns of edema and accumulation of the PMN marker enzyme, myeloperoxidase (MPO), were examined following application of tetradecanoylphorbol acetate (TPA) to mouse ears. After application of 2.5 micrograms TPA, edema peaked at 6 hr, while MPO activity peaked at 24 hr. Pharmacological agents with defined mechanisms of action, delivered orally or topically, were assessed for effects on these responses. For oral administration, compounds were delivered 1 hr before and 6 hr after TPA and for topical administration compounds were delivered at 15 min and 6 hr after TPA. Topical and oral corticosteroids inhibited both edema and MPO accumulation. Cyclooxygenase and lipoxygenase inhibitors were very effective against MPO accumulation but were either inactive or moderately active vs edema. Anti-histamine/anti-serotonin agents had little effect on edema, but could inhibit or exacerbate MPO accumulation depending on dose and route of administration. Topically applied histamine itself did not effect TPA-induced edema, but markedly suppressed MPO accumulation. Acetone, the vehicle, when topically applied between 0.5 and 2 hr after TPA inhibited MPO accumulation by 60-80%, but had little effect on edema. Acetone applied before 0.5 hr or after 2 hr had no effect on either parameter. These results indicate that in the TPA-induced ear inflammation model the MPO response at 24 hr may be a useful additional indicator of drug activity.

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Section: Introductionmentioning

confidence: 99%

“…Rat passive cutaneous anaphylaxis (PCA) is the most widely used test for potential antiallergic drugs [Garland et al, 1979;Krell and Chakrin, 19801. In this model of allergic reactions, skin mast cells become sensitized after local injection of exogenous, specific IgEantibodies. Subsequent contact with the corresponding allergen activates these mast cells, and the released mediators cause increased permeability of the microcirculation, which is reflected in well-defined areas of extravasating blue dye [Watanabe and Ovary, 19771. Major mediators of rat mast cells are histamine and serotonin [Bhattacharya and Lewis, 19561 and antagonists of these amines reduce the intensity of PCA reactions .…”

Section: Introductionmentioning

confidence: 99%

Interaction of astemizole and other drugs with passive cutaneous anaphylactic and histamine‐, serotonin‐, and compound 48/80‐induced skin reactions in the rat: A Procedure to determine anti‐allergic effectiveness

Awouters

Niemegeers

Janßen

1985

Drug Development Research

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Awouters, F., C.J.E. Niemegeers and P.A.J. Janssen: Interaction of astemizole and other drugs with passive cutaneous anaphylactic and histamine-, serotonin-, and compound 48180-induced skin reactions in the rat. A procedure to determine anti-allergic effectiveness. Drug Dev. Res. 5:137-145, 1985. Passive cutaneous anaphylactic (PCA) reactions in rats were induced simultaneously with skin reactions to intradermally injected histamine, serotonin, and compound 48/80. In this test compounds with widely different pharmacological profiles were studied to evaluate the significance of anti-allergic activity. Five cromoglycatelike drugs, injected i.v. 5 min before antigen challenge, were either devoid of activity or significant inhibition of PCA reactions was associated to inhibition of histamine and compound 48/80 reactions. Two histamine HI-antagonists, astemizole and ketotifen; the serotonin S2-antagonist ketanserin; and the a-adrenergic blocking agent prazosin were tested over a wide dose range 2 hr after S.C. administration. Prazosin, as a result of systemic hemodynamic effects, significantly inhibited the four reactions (primarily PCA), but complete inhibition was not obtained. Ketanserin primarily inhibited serotonin reactions, and inhibition of other reactions required high doses. Ketotifen was a very potent and apparently competitive inhibitor of histamine reactions, with a significant effect on PCA and compound 48/80 reactions. Astemizole primarily inhibited histamine and PCA reactions; complete inhibition was reached for the Received final version July 12, 1984; accepted July 30, 1984. Address reprint requests to F. Awouters, Department of Pharmacology, Janssen Pharmaceutica, B-2340 Beerse, Belgium. 138Awouters, Niemegeers, and Janssen four reaction types. In terms of a practical definition of anti-allergic drugs, i.e., compounds capable of fully suppressing the consequences of allergen challenge in the absence of nonspecific systemic effects, astemizole appears to be a prototype.

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Inhibitors of the Release of Anaphylactic Mediators

Cited by 4 publications

References 166 publications

Differential effects of anti-allergic compounds on peritoneal mast cells of the rat, mouse and hamster

Differential effects of anti-allergic compounds on peritoneal mast cells of the rat, mouse and hamster

Edema and cell infiltration in the phorbol ester-treated mouse ear are temporally separate and can be differentially modulated by pharmacologic agents

Interaction of astemizole and other drugs with passive cutaneous anaphylactic and histamine‐, serotonin‐, and compound 48/80‐induced skin reactions in the rat: A Procedure to determine anti‐allergic effectiveness

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