title: Antiallergic action of betotastine besilate (TAU-284) in animal models: A comparison with ketotifen.
abstract: The effects of betotastine besilate (betotastine: TAU-284), a novel antiallergic drug, on homologous passive cutaneous anaphylaxis (PCA), mediator-induced cutaneous reaction, antigen-induced asthmatic responses and platelet-activating factor (PAF)-induced airway eosinophilia in several animal models, were compared to ketotifen. Betotastine (0.1 mg/kg, p.o.) and ketotifen (1 mg/kg, p.o.) inhibited both rat PCA and histamine-induced cutaneous reaction, whereas they showed little effect on serotonin-induced cutaneous reaction. Betotastine (0.3 mg/kg, p.o.) and ketotifen (1 mg/kg, p.o. ) significantly inhibited antigen-induced bronchoconstriction in guinea pigs which had been passively sensitized with guinea pig IgE antibody. In actively sensitized guinea pigs, the immediate and late phase increase in airway resistance (Rrs) were observed within 5 min and between 4 and 7 h after the aeroantigen challenge. Betotastine (1 mg/kg, p.o.) inhibited both responses. Ketotifen (1 mg/kg, p.o.) inhibited the immediate phase response, but did not affect the late phase response. Exposure of guinea pigs to aerosolized PAF increased the number of eosinophils in bronchoalveolar lavage fluid 24 h after the stimulation. Betotastine (3-10 mg/kg, p.o.) dose-dependently inhibited PAF-induced accumulation of eosinophils in the bronchoalveolar cavity. In contrast, cetirizine (10 mg/kg, p.o.) showed a tendency to inhibit eosinophil accumulation, and ketotifen (10 mg/kg, p.o.) and terfenadine (10 mg/kg, p.o.) did not have any affect. These results indicate that betotastine could be useful in the treatment of allergic disease such as bronchial asthma.
authors.affiliation: Lead Generation Research Laboratory, Tanabe Seiyaku Co. Ltd, Osaka, Japan. ueno@tanabe.co.jp
authors.forename: M
authors.initials: M
authors.lastname: Ueno
authors.forename: N
authors.initials: N
authors.lastname: Inagaki
authors.forename: H
authors.initials: H
authors.lastname: Nagai
authors.forename: A
authors.initials: A
authors.lastname: Koda
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy; D016084:Bronchoconstriction / Q000187:drug effects; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000188:drug therapy; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D005260:Female; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006967:Hypersensitivity / Q000188:drug therapy*; D007665:Ketotifen / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D010972:Platelet Activating Factor / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018926:Anti-Allergic Agents; D006634:Histamine H1 Antagonists; D010880:Piperidines; D010972:Platelet Activating Factor; D011725:Pyridines; C108476:bepotastine; D007665:Ketotifen