Pharmacological Studies on the Novel Antiallergic Drug HQL-79: I. Antiallergic and Antiasthmatic Effects in Various Experimental Models

• Published in: Japanese journal of pharmacology 1998, Vol.78(1), pp.1-10
• Main Authors: Nobutoshi, Matsushita, Masanori, Hizue, Kosuke, Aritake, Kumi, Hayashi, Ayumi, Takada, Kazuhiko, Mitsui, Masatoshi, Hayashi, Ichiro, Hirotsu, Yoshiyuki, Kimura, Tadato, Tani, Hiromichi, Nakajima
• Format: Article
• Language: English
• Subjects: Airway inflammation; Animals; Anti-Allergic Agents - pharmacology; Anti-Asthmatic Agents - pharmacology; Antiallergic drug; Antigens - pharmacology; Bronchoconstriction - drug effects; Bronchoconstriction - immunology; Capillary Permeability - drug effects; Delayed-type hypersensitivity; Dibenzazepines - pharmacology; Disease Models, Animal; Dose-Response Relationship, Drug; Guinea Pigs; Histamine H1 Antagonists - pharmacology; HQL-79; Hypersensitivity, Delayed - prevention & control; Imidazoles - pharmacology; Ketotifen - pharmacology; Late asthmatic response; Leukocytes - drug effects; Leukocytes - pathology; Male; Mice; Mice, Inbred ICR; Nasal Mucosa - physiology; Passive Cutaneous Anaphylaxis - drug effects; Piperidines - pharmacology; Rats; Rats, Wistar; Respiratory Hypersensitivity - prevention & control
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1254/jjp.78.1

The effects of oral administration of 4-benzhydryloxy-1-{3-(1H-tetrazol-5-yl)-propyl}piperidine (HQL-79), a newly synthesized antiallergic drug, in various experimental allergic and asthmatic models were investigated. HQL-79 markedly inhibited immediate hypersensitivity reactions such as passive cutaneous anaphylaxis in rats, antigen-induced bronchoconstriction and nasal vascular permeability in actively sensitized guinea pigs, like epinastine and ketotifen did. Airway eosinophilia in repeatedly antigen-exposed guinea pigs was suppressed by chronic administration of HQL-79 for 2 weeks. In another experiment, the antigen-induced late asthmatic response (LAR) in metyrapone-treated guinea pigs was also ameliorated by chronic treatment with HQL-79. Moreover, HQL-79 partially inhibited the toluene diisocyanate-induced delayed-type hypersensitivity (DTH) reaction in mice when administered chronically during the immunization period. The corticosteroid dexamethasone inhibited the airway inflammatory responses in guinea pigs and the DTH in mice. These results indicate that HQL-79 has potent inhibitory effects on the immediate hypersensitivity reactions, and when administered chronically, it also inhibits airway eosinophilia, LAR and DTH, similarly to corticosteroids.