Effect of antihistamines on antigen-induced increase of rat tracheal mucous gel layer thickness.
The effect of orally administered H1 and H2 antihistamines on antigen-induced changes in tracheal mucous gel layer thickness of actively sensitized rats was determined. Cimetidine and ranitidine, H2 antagonists, produced dose-dependent inhibition of antigen-induced increase in gel thickness at doses ranging from 0.32 to 3.16 and from 0.10 to 1.0 mg/kg, respectively. H1 antagonists - like chlorpheniramine, diphenhydramine, and pyrilamine which possess anticholinergic properties - tended to enhance the antigen-induced gel thickening in a dose-dependent fashion, while astemizole and terfenadine had no effect. These data indicate that an antigen-induced increase of rat tracheal mucous gel layer thickness may result from stimulation of the H2 receptor, while histamine operating at the H1 receptor does not play a role. Therefore, an antihistamine that possesses both H1 and H2 antagonist properties while lacking anticholinergic properties appears to be the most appropriate for use in patients with asthma and associated bronchorrhea.
Yanni
J M
JM
Department of Pharmacology, A.H. Robins Research Laboratories, Richmond, Va.
Foxwell
M H
MH
Whitman
L L
LL
D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D005782:Gels; D006023:Glycoproteins / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000008:administration & dosage*; D006635:Histamine H2 Antagonists / Q000008:administration & dosage*; D006636:Histamine Release / Q000187:drug effects; D008297:Male; D009093:Mucus / Q000187:drug effects / Q000378:metabolism*; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*
D000941:Antigens; D005782:Gels; D006023:Glycoproteins; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; C047874:gastric mucus glycoproteins; D010047:Ovalbumin