The activity of sodium cromoglycate analogues in human lung in vitro: a comparison with rat passive cutaneous anaphylaxis and clinical efficacy

British Journal of Pharmacology
M K Church, C F Gradidge

Abstract

1 Eleven analogues of sodium cromoglycate have been tested for their ability to suppress histamine release induced by anti-IgE from passively sensitized human lung fragments in vitro. 2 With the exception of WY 16922, which released histamine at high concentrations, all inhibited histamine release in a linear dose-related manner. 3 The analogues were 30 to 1500 times more potent than sodium cromoglycate. However, their regression slopes of activity upon log-concentration were only one-third as steep as that for sodium cromoglycate, indicating a possible difference in their mechanism of action. 4 In comparison with sodium cromoglycate, the analogues were more potent in human lung than in rat passive cutaneous anaphylaxis (PCA); there was no quantitative correlation between potencies in the two tests. 5 The human lung model is not predictive of anti-asthmatic activity in man as the six analogues tested clinically are less effective than sodium cromoglycate. 6 These results throw doubt on the use of models of mast cell degranulation in the search for anti-allergic drugs and, possibly, on the relative importance of mast cell degranulation in the pathogenesis of asthma.

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Related Concepts

Metazoa
Vicrom
Histamine Release
Immunoglobulin E
Lung
Passive Cutaneous Anaphylaxis
Rats, Laboratory
In Vitro [Publication Type]

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