Jpn. J. Pharmacol. 75 (4), 347-353 (1997)

Effects of a Specific Cysteinyl Leukotriene Antagonist, Pranlukast, on Antigen-Induced Cysteinyl Leukotriene-Mediated Rhinitis in Guinea Pigs

Manabu Fujita, Yasuo Yonetomi, Hiroshi Takeda, Naoki Nakagawa, Kazuhito Kawabata (*) and Hiroyuki Ohno

Minase Research Institute, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618, Japan
(*) To whom correspondence should be addressed.

Abstract: To examine the effects of a specific cysteinyl leukotriene (cysLT) antagonist, pranlukast, on allergic rhinitis, antigen-induced rhinitis in guinea pigs was modified by pretreatment with an cyclooxygenase inhibitor (indomethacin) followed by an H1-blocker (pyrilamine). Intranasal ovalbumin (OVA) administration in actively sensitized guinea pigs resulted in concentration-dependent increases in nasal permeability and nasal airway resistance (NAR). Although pyrilamine (1 mg/kg, i.v.) abolished these antigen-induced changes, pretreatment with indomethacin (5 mg/kg, i.v.) followed by pyrilamine enhanced these responses to a degree similar to that observed with OVA challenge alone. Analyses of nasal perfusate in indomethacin/pyrilamine-pretreated animals showed that cysLTs increased by 270.8%, whereas thromboxane B2 decreased by 88.3% as compared with those on challenged with OVA alone. Oral administration of pranlukast (1 - 10 mg/kg) dose-dependently prevented increases in nasal permeability and NAR of indomethacin/pyrilamine-pretreated animals. However, an anti-allergic agent, azelastine, did not affect these responses. These results indicate that pranlukast suppresses antigen-induced cysLT-mediated responses of allergic rhinitis in actively sensitized guinea pigs. A cysLT antagonist, pranlukast, may thus prevent cysLT-mediated symptoms of allergic rhinitis.

Keywords: Pranlukast, Rhinitis, Leukotriene, Allergic, Ovalbumin

Copyrightę The Japanese Pharmacological Society 1997

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