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