Accumulation of granulocytes in the lung and skin of guinea pigs. Inhibition by the anti-H1 antiallergic agent epinastine.
The aim of this study was to investigate whether the antiallergic/H1-antagonistic drug epinastine (WAL 801, Alesion, CAS 108929-04-0) inhibited inflammatory granulocyte infiltration in respiratory or dermal tissue. A late-phase bronchial eosinophilia was induced in sensitized and challenged guinea pigs, and a skin chamber technique was developed for assessing leukotriene-B4 (LTB4) induced transdermal chemotaxis in vivo in this species. Oral epinastine as well as the reference compounds beta-methasone and the LTB4-receptor antagonist 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy) propoxy]-3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid (ADCA) demonstrated a dose-dependent inhibition of granulocyte accumulation. The rank order of oral activity was epinastine > betamethasone > ADCA for bronchial eosinophilia and betamethasone > epinastine = ADCA for transdermal chemotaxis. These animal studies suggest a non-antihistamine activity of epinastine which may contribute to its clinical efficacy as an antiallergic drug.
Department of Pharmacology, Boehringer Ingelheim KG, Ingelheim/Rhein, Fed. Rep. of Germany.
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Fügner
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Meissner
D000818:Animals; D001623:Betamethasone / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003984:Dibenzazepines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006098:Granulocytes / Q000187:drug effects*; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D008297:Male; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D011657:Pulmonary Eosinophilia / Q000139:chemically induced / Q000473:pathology; D012867:Skin / Q000166:cytology* / Q000187:drug effects
D003984:Dibenzazepines; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D007975:Leukotriene B4; D001623:Betamethasone; C053090:epinastine