title: Effect of ZCR-2060, an antiallergic agent, on antigen-induced immediate- and late-phase increases in airway resistance in sensitized guinea pigs.
abstract: The effect of 2-[2-[4-(diphenylmethyl)-1-piperadinyl]ethoxy] benzoic acid maleate (ZCR-2060) on passive systemic anaphylaxis (PSA) and antigen-induced immediate- and late-phase increase in airway resistance (Rrs) in either passively or actively sensitized guinea pigs were investigated. ZCR-2060 inhibited PSA in guinea pigs. ID50 values of ZCR-2060, ketotifen, terfenadine and cetirizine on PSA were 0.03, 0.02, 0.8 and 0.3 mg/kg, respectively, when administered orally 1 h before the antigen challenge. The protective effect of ZCR-2060 was observed until 12 h before the antigen challenge. Aeroantigen-induce immediate increase in Rrs in passively sensitized guinea pigs with and without metyrapone treatment was inhibited by ZCR-2060, ketotifen, terfenadine and cetirizine. In contrast, prednisolone did not affect the aeroantigen-induced immediate increase in Rrs in animals not treated with metyrapone, but significantly inhibited the metyrapone-induced enhanced immediate response. In actively sensitized animals, the immediate- and late-phase increases in Rrs were observed within 30 min and between 3 and 8 h after the aeroantigen challenge. Pretreatment with metyrapone accelerated both antigen-induced responses. ZCR-2060 (1 mg/kg) significantly inhibited both responses. Ketotifen (1 mg/kg), terfenadine (10 mg/kg) and prednisolone (10 mg/kg) significantly the inhibited the late-phase response, but did not affect the immediate-phase response. In contrast, Cetirizine (10 mg/kg) did not affect either response. The effect of ZCR-2060 on late-phase response was stronger than that of ketotifen, terfenadine and cetirizine, and was almost the same as that of prednisolone. These results suggest that ZCR-2060 has a potent protective effect on immediate- and late-phase increases in Rrs.
authors: Department of Pharmacology, Gifu Pharmaceutical University, Japan.
authors: T
authors: T
authors: Abe
authors: K
authors: K
authors: Yoshida
authors: T
authors: T
authors: Omata
authors: Y
authors: Y
authors: Segawa
authors: K
authors: K
authors: Matsuda
authors: H
authors: H
authors: Nagai
mesh_terms: D000403:Airway Resistance / Q000187:drug effects*; D000707:Anaphylaxis / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D001565:Benzoates / Q000627:therapeutic use*; D001980:Bronchi / Q000503:physiopathology; D017332:Cetirizine / Q000627:therapeutic use; D005260:Female; D006168:Guinea Pigs; D007665:Ketotifen / Q000627:therapeutic use; D008797:Metyrapone / Q000494:pharmacology; D010047:Ovalbumin / Q000494:pharmacology; D010880:Piperidines / Q000627:therapeutic use*; D011239:Prednisolone / Q000494:pharmacology; D016593:Terfenadine / Q000627:therapeutic use
chemical_list: D001565:Benzoates; D010880:Piperidines; C091433:ZCR 2060; D016593:Terfenadine; D010047:Ovalbumin; D011239:Prednisolone; D007665:Ketotifen; D017332:Cetirizine; D008797:Metyrapone