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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

1985; Wiley; Volume: 5; Issue: 2 Linguagem: Inglês

10.1002/ddr.430050206

1098-2299

F. Awouters, C. J. E. Niemegeers, Paul A. J. Janssen,

Food Allergy and Anaphylaxis Research

Abstract 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 H 1 ‐antagonists, astemizole and ketotifen; the serotonin S 2 ‐antagonist ketanserin; and the α‐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 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.