Comparison of anti-allergic activities of the histamine H1 receptor antagonists epinastine, ketotifen and oxatomide in human leukocytes.
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.
Mita
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Clinical Research Center, National Sagamihara Hospital, Kanagawa, Japan.
Shida
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D001249:Asthma / Q000097:blood; D000001:Calcimycin / Q000494:pharmacology; D003984:Dibenzazepines / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy*; D007093:Imidazoles / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000502:physiology; D066298:In Vitro Techniques; D007665:Ketotifen / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D017997:Leukotriene C4 / Q000096:biosynthesis; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000096:biosynthesis
D003984:Dibenzazepines; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D010879:Piperazines; D010972:Platelet Activating Factor; D017997:Leukotriene C4; D007073:Immunoglobulin E; D000001:Calcimycin; C015408:oxatomide; C053090:epinastine; D007665:Ketotifen