calcimycin and epinastine

Eosinophils are prominent inflammatory cells which play a critical role in the pathogenesis of allergic diseases and bronchial asthma. The aim of this experiment was to examine the effects of oxatomide (CAS 60607-34-3, KW-4354), an antiallergic agent, on oxygen-radical generation and peptide-leukotriene (p-LT) release from guinea pig eosinophils. Ketotifen (CAS 345080-13-7) and epinastine (CAS 80012-43-7) were used as reference drugs. Eosinophils were isolated from the peritoneal exudate of guinea pigs, in which peritoneal eosinophilia had been induced by injection of horse serum. Oxygen-radicals were measured with luminol-dependent chemiluminescence and p-LT release was measured with enzyme immunoassay. When eosinophils were stimulated with phorbol miristate acetate, oxatomide and ketotifen inhibited the oxygen-radical generation with a concentration required for 50% inhibition (IC50) of 11.7 mumol/l and 28.4 mumol/l. Oxatomide, ketotifen or epinastine showed an inhibition of oxygen-radical generation induced by calcium ionophore A-23187 and the IC50 value was 11.3 mumol/l for oxatomide, 15.1 mumol/l for ketotifen and 27.3 mumol/l for epinastine, suggesting that oxatomide is a more potent inhibitor of oxygen-radical generation than ketotifen and epinastine. Oxatomide also inhibited p-LT release induced by calcium ionophore A-23187 (IC50, 9.83 mumol/l). Ketotifen and epinastine only weakly inhibited p-LT release. These results suggest that oxatomide may regulate inflammatory diseases, such as bronchial asthma, through suppression of eosinophil function.

Topics: Animals; Anti-Allergic Agents; Calcimycin; Dibenzazepines; Eosinophils; Free Radicals; Guinea Pigs; Histamine H1 Antagonists; Imidazoles; In Vitro Techniques; Ketotifen; Leukotrienes; Luminescent Measurements; Male; Oxygen Consumption; Piperazines

Eosinophils are believed to be one of the important sources of cytokines at the site of allergic inflammation. A novel antiallergic agent epinastine showed a dose- and time-dependent suppressive effect on IL-8, one of the chemokines for eosinophils, released from eosinophils isolated from atopic diseases. The time-dependent accumulation of IL-8 inhibited by cycloheximide and the evaluation of the IL-8 mRNA levels by reverse transcriptase-polymerase chain reaction suggested that its action occurred in the posttranscriptional processes. It was suggested that epinastine might prevent the autocrine cycle for recruitment of human eosinophils by inhibiting IL-8 release from these cells.

Topics: Calcimycin; Cells, Cultured; Chemokine CCL5; Dibenzazepines; DNA Primers; Enzyme-Linked Immunosorbent Assay; Eosinophils; Histamine H1 Antagonists; Humans; Imidazoles; Interleukin-8; Kinetics; Polymerase Chain Reaction; Transcription, Genetic

The effects of three histamine H1 receptor antagonists, epinastine (CAS 80012-43-7, WAL-801 CL), ketotifen (CAS 34580-13-7) and oxatomide (CAS 60607-34-3), on mediator release have been studied in human peripheral leukocytes. When leukocytes from asthmatic patients sensitive to mite were stimulated with the allergen, epinastine inhibited histamine release with a concentration required for 50% inhibition (IC50) of 3 x 10(-5) mol/l and leukotriene C4 generation. On the other hand, ketotifen or oxatomide showed little inhibiting effect on histamine release elicited with the allergen. When the cells were stimulated with calcium ionophore A23187, epinastine failed to inhibit histamine release and leukotriene C4 generation. Oxatomide caused a concentration related inhibition of calcium ionophore-induced histamine release with the IC50 value of 5 x 10(-5) mol/l. Ketotifen or oxatomide also showed an inhibition of leukotriene C4 generation induced by calcium ionophore in a dose-dependent manner and the IC50 value was 6 x 10(-6) mol/l for oxatomide and 8 x 10(-5) mol/l for ketotifen, suggesting that oxatomide is a more potent inhibitor of leukotriene C4 generation than ketotifen. These results indicate that epinastine inhibits IgE-mediated histamine release and LTC4 generation, and oxatomide has a capacity to inhibit calcium ionophore-induced mediator release from human leukocytes. Additionally, when platelet activating factor was quantitated by radioimmunoassay in the supernatant and the cell pellet after ionophore stimulation, epinastine inhibited the formation and the secretion in a dose-dependent manner.

Topics: Asthma; Calcimycin; Dibenzazepines; Histamine H1 Antagonists; Humans; Hypersensitivity; Imidazoles; Immunoglobulin E; In Vitro Techniques; Ketotifen; Leukocytes; Leukotriene C4; Neutrophils; Piperazines; Platelet Activating Factor