Lever, R., Hefni, A., Moffatt, J.D., Paul, W. and Page, C.P. (2007) Effect of tecastemizole on pulmonary and cutaneous allergic inflammatory responses. Clinical & Experimental Allergy, 37 (6). p. 909. 10.1111/j.1365-2222.2007.02730.x.
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Background Tecastemizole, a major metabolite of astemizole, is a potent and selective H1 receptor antagonist. Evidence suggests that this and certain other H1 receptor antagonists may possess anti-inflammatory effects that are, in some cases, independent of H1 receptor antagonism. Objective The aim of this study was to investigate the anti-inflammatory effects of tectastemizole in models of allergic inflammation. Methods Effects of tecastemizole were assessed in a murine model of allergic lung inflammation, in passive cutaneous anaphylaxis (PCA) responses in guinea-pig skin and in in vitro assays measuring endothelial adhesion molecule expression and leucocyte–endothelial adhesion. Results Tecastemizole inhibited antigen-induced eosinophil recruitment to the lungs of allergic mice in a dose-dependent manner. Furthermore, combination of a sub-effective dose of tecastemizole, combined with a sub-effective dose of dexamethasone inhibited eosinophil accumulation in this model. Plasma extravasation in PCA reactions was inhibited by tecastemizole, although by a mechanism that would appear to be H1 receptor-dependent. Cytokine-induced endothelial intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression, as well as mononuclear cell adhesion to human umbilical vein endothelial cells was inhibited by tecastemazole in a manner independent of H1 receptor antagonism. Conclusion These data suggest that tecastemizole may have H1 receptor-independent effects in inhibiting late-phase inflammatory responses, while acute responses appear to be inhibited in a H1 receptor-dependent manner. Furthermore, our data suggest an important potential steroid-sparing role for such drugs in the treatment of allergic inflammatory conditions.
|Uncontrolled Keywords:||adhesion;allergy;antihistamine;asthma;endothelium;eosinophil;glucocorticosteroid;H1 receptor;histamine;PCA|
|Departments, units and centres:||Department of Pharmacology > Department of Pharmacology|
|Journal or Publication Title:||Clinical & Experimental Allergy|
|Deposited By:||Library Staff|
|Deposited On:||10 May 2012 12:27|
|Last Modified:||10 May 2012 12:27|
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