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Effects of ZCR-2060 on allergic airway inflammation and cell activation in guinea-pigs.

Abstract
The effects of 2-(2-(4-(diphenylmethyl)-1-piperadinyl) ethoxy) benzoic acid malate (ZCR-2060) on allergic airway inflammation and inflammatory cell activation in guinea-pigs were studied. Allergic airway inflammation was induced by inhalation of antigen into actively-sensitized animals and the increase in inflammatory cells into bronchoalveolar lavage fluid (BALF) was measured. Aeroantigen-induced infiltration of inflammatory cells, especially eosinophils and neutrophils, in BALF gradually increased, and reached a peak at 6 or 9 h after the challenge. ZCR-2060 (1 mg kg-1 p.o.) clearly inhibited the increase of eosinophil numbers in BALF. Moreover, the effect of ZCR-2060 on inflammatory cell activation in terms of chemotaxis and superoxide generation in-vitro was studied. ZCR-2060 (10(-6)-10(-4) M) inhibited the platelet-activating factor (PAF)-induced chemotaxis of eosinophils and neutrophils, but did not inhibit the leukotriene B4-induced chemotaxis of eosinophils and the formyl-Met-Leu-Phe-induced chemotaxis of neutrophils. PAF-induced superoxide anion generation by eosinophils, neutrophils and alveolar macrophages was inhibited by ZCR-2060 (10(-6)-10(-4) M). However, ZCR-2060 did not affect phorbol myristate acetate-induced superoxide anion generation by eosinophils, neutrophils and alveolar macrophages. These results indicate that ZCR-2060 inhibits allergic airway inflammation, and PAF-induced inflammatory cell activation in guinea-pigs. ZCR-2060 may prove useful for the treatment of allergic airway inflammation or allergic disorders, especially inflammatory cell infiltration and activation.
AuthorsT Abe, K Yoshida, T Omata, Y Segawa, K Matsuda, H Nagai
JournalThe Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 46 Issue 11 Pg. 876-82 (Nov 1994) ISSN: 0022-3573 [Print] ENGLAND
PMID7897591 (Publication Type: Journal Article)
Chemical References
  • Benzoates
  • Piperidines
  • Platelet Activating Factor
  • ZCR 2060
  • Superoxides
  • Leukotriene B4
  • N-Formylmethionine Leucyl-Phenylalanine
  • Tetradecanoylphorbol Acetate
Topics
  • Animals
  • Benzoates (pharmacology)
  • Bronchoalveolar Lavage Fluid (cytology)
  • Chemotaxis, Leukocyte (drug effects)
  • Eosinophils (drug effects, metabolism)
  • Guinea Pigs
  • Inflammation (drug therapy, pathology)
  • Leukotriene B4 (metabolism)
  • Macrophages, Alveolar (drug effects, metabolism)
  • Male
  • N-Formylmethionine Leucyl-Phenylalanine (pharmacology)
  • Neutrophils (drug effects, metabolism)
  • Piperidines (pharmacology)
  • Platelet Activating Factor (pharmacology)
  • Respiratory Hypersensitivity (drug therapy, pathology)
  • Superoxides (metabolism)
  • Tetradecanoylphorbol Acetate (pharmacology)

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