In-vitro-Untersuchungen mit Terfenadin und verschiedenen Derivaten zur Mediatorfreisetzung aus menschlichen Hautmastzellen, eosinophilen und basophilen Granulozyten

Translated title of the contribution: In vitro studies on the effects of terfenadine and different derivatives on mediator release from human skin mast cells, eosinophilic and basophilic granulocytes

U. Ramachers, C. Hiller, M. Nitschke, D. Dieckmann, M. Q. Zhang, H. Timmerman, B. F. Gibbs, I. B. Vollrath, C. Albrecht, U. Amon*

*Corresponding author for this work
3 Citations (Scopus)

Abstract

H1 receptor antagonists are used as symptomatic therapy in a number of allergic diseases such as urticaria, asthma, atopic dermatitis and hayfever. In recent years, there has been a growing interest in the suppressive effects of H1 receptor antagonists on mediator release from inflammatory cells, other than the H1 receptor blocking effects of these drugs. The aim of this study was to investigate the potential inhibitory effects of terfenadine on human skin mast cells, eosinophils and basophils that had been stimulated by a number of different secretagogues. Furthermore, chemical derivatives of terfenadine were compared so that possible structure-activity relationships could be ascertained. Terfenadine inhibited anti-IgE, concanavalin A, and grass pollen-activated basophils with 44.5±6,5%, 67.9±6.2% and 44.0±9.9% inhibition of histamine release respectively at 100 μM of the drug, whereas no effect was observed for phorbol ester-(TPA)-induced release. Additionally, anti-IgE-stimulated LTC4 production from basophils was strikingly inhibited (up to 95%) due to the action of terfenadine. In human skin mast cells terfenadine effectively inhibited anti-IgE, A23187 and substance P-mediated histamine release dose-dependently, although this effect was only observed following 12 hours preincubation with the drug before stimulation. However, no effect was seen in PGD2 production due to the action of the drug. Terfenadine was not effective in inhibiting mediator release from eosinophils. The main metabolite of terfenadine, MDL 16455, was less effective than terfenadine itself. A comparison between the molecular structures of various terfenadine derivatives appeared to show a relationship between their antiallergenic activity and the degree of lipophilicity. Thus, increased lipophilicity of some terfenadine derivatives may possibly produce cell stabilizing effects due to plasma membrane association with these compounds.

Translated title of the contributionIn vitro studies on the effects of terfenadine and different derivatives on mediator release from human skin mast cells, eosinophilic and basophilic granulocytes
Original languageGerman
JournalAllergo Journal
Volume5
Issue number8
Pages (from-to)447-452
Number of pages6
ISSN0941-8849
Publication statusPublished - 1996

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