Nobutoshi Matsushita (#), Masanori Hizue, Kosuke Aritake, Kumi Hayashi,
Ayumi Takada, Kazuhiko Mitsui, Masatoshi Hayashi, Ichiro Hirotsu, Yoshiyuki
Kimura, Tadato Tani and Hiromichi Nakajima
New Drug Research Department, High Quality-Life Research Laboratories,
Bio-Medical Division, Sumitomo Metal Industries, Ltd., 3-5 Hikaridai, Seika-cho,
Souraku-gun, Kyoto 619-0237, Japan
(#) Present address for correspondence: Pharmacological Research Group,
Bioclinical Research, Rohto Pharmaceutical Co., Ltd., 1-8-1, Tatsumi-nishi,
Ikuno-ku, Osaka 544-8666, Japan
Abstract: 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.
Keywords: Antiallergic drug, Late asthmatic response, Airway inflammation,
Delayed-type hypersensitivity, HQL-79