Levocabastine is a potent H 1 -receptor antagonist which provides long-acting antihistaminic and antiallergic activities in experimental animals. 1,2) In experimental allergic conjunctivitis in guinea pigs, levocabastine causes the inhibition of antigen-and histamine-induced conjunctivitis, and these effects are superior to those of cromolyn sodium.1) Clinical studies also revealed that levocabastine is well-tolerated and is at least as effective as cromolyn sodium for the treatment of pollen-provoked conjunctivitis.3,4) Abelson et al. 5) also found that levocabastine is significantly more effective than cromolyn sodium in inhibiting itching, hyperemia, eyelid swelling, chemosis and tearing in allergic conjunctivitis induced by ocular allergen challenge.On the other hand, the treatment of conjunctivitis associated with pollinosis is at present carried out by antihistamines either alone or in combination with alpha-adrenergic agents and mast cell stabilizers. 6) Pemirolast is a drug that exhibits potent antiallergic activity compared with cromolyn sodium.7) In addition, it inhibits histamine release induced by immunological and non-immunological stimuli, and this effect is more potent than that of cromolyn sodium and tranilast. Therefore, it is possible to obtain a more effective medical treatment of allergic conjunctivitis if levocabastine and pemirolast are administered simultaneously. In the present study, we investigated the effect of the simultaneous use of levocabastine and pemirolast on eye scratching behavior and allergic symptoms in allergic rat conjunctivitis models which we recently developed.
8) MATERIALS AND METHODS
AnimalsSix weeks-old male Wistar rats were obtained from Japan SLC, Inc., Shizuoka, Japan. The animals were housed in an air-conditioned room maintained at 24Ϯ2°C with humidity of 55Ϯ15%. They were given standard laboratory rodent chow (Oriental Yeast, Tokyo, Japan) and water ad libitum.Reagents The following reagents were obtained from the sources shown in parentheses: egg albumin (Grade VII; crystallized and lyophilized, essentially salt-free, Sigma, St. Louis, MO, U.S.A.), aluminum hydroxide hydrate gel (alum, LSL, Tokyo, Japan), and Evans blue (Wako, Tokyo, Japan). Bordetella pertussis inactive microorganism suspension (B. pertussis) was kindly provided by the Kitasato Institute Research Center for Biologicals, Saitama, Japan. The following drugs were purchased from the companies indicated: 0.025% levocabastine hydrochloride eye drops (levocabastine, Livostin eye drops, Santen Pharmaceutical Co., Osaka, Japan) and 0.1% pemirolast potassium ophthalmic solution (pemirolast, Alegysal ophthalmic solution, Santen Pharmaceutical Co., Osaka, Japan). Levocabastine and pemirolast were instilled at 5 and 15 min, respectively, before antigen challenge into the bilateral eyes at 5 ml/site.Sensitization The rats were sensitized by injection of 0.6 ml of physiological saline containing egg albumin (1 mg), alum (2 mg) and 10 10 B. pertussis into the four footpads on the first day. Five days later, t...