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Demonstration of Inhibition of Mediator Release From Human Mast Cells by Azatadine BaseIn Vivo and In Vitro Evaluation
Alkis G. Togias, MD;
Robert M. Naclerio, MD;
Jane Warner, PhD;
David Proud, PhD;
Anne Kagey-Sobotka, PhD;
Indira Nimmagadda;
Philip S. Norman, MD;
Lawrence M. Lichtenstein, MD, PhD
JAMA. 1986;255(2):225-229.
Abstract
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In vitro experimentation using dispersed human lung mast cells demonstrated that azatadine base, a compound with known H1-antihistamine properties, inhibited anti-IgE-induced release of histamine and leukotriene C4 by 45% and 85%, respectively. To assess the clinical relevance of these findings and to compare in vitro mast cell data with results obtained in vivo, nasally instilled azatadine was tested in a double-blind, placebo-controlled clinical trial in which nasal challenges with antigen were performed on eight allergic individuals. Pretreatment with azatadine significantly suppressed the number of sneezes following antigen challenge and inhibited the associated elevations in histamine, kinins, and enzyme(s) hydrolyzing the artificial substrate N- -tosyl-L-arginine-methyl-ester in nasal secretions, whereas placebo was inactive. Hence, we showed agreement between our in vitro and in vivo experimental models of the allergic reaction. Topical application of azatadine base has the potential to become an effective antiallergic treatment.
(JAMA 1986;255:225-229)
Author Affiliations
From the Departments of Medicine (Drs Togias, Warner, Proud, Kagey-Sobotka, Norman, and Lichtenstein and Ms Nimmagadda) and Otolaryngology (Dr Naclerio), The Johns Hopkins University School of Medicine at The Good Samaritan Hospital, Baltimore.
Footnotes
Reprint requests to Division of Clinical Immunology, The Johns Hopkins University School of Medicine at The Good Samaritan Hospital, 5601 Loch Raven Blvd, Baltimore, MD 21239 (Dr Togias).
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