Anti-allergic effects of ketanserin on animal models of allergic reactions

The aim of the present study is to investigate the effect of ketanserin, a potent and selective S2-serotonergic antagonist, on some anaphylactic reactions in mice, rats and guinea-pigs. Ketanserin (1 and 5 mg/kg) inhibited both IgE antibody-mediated 48 hr homologous passive cutaneous anaphylaxis and IgG antibody-mediated 1.5 hr homologous passive cutaneous anaphylaxis in mice. In histamine-, serotonin- and LTC4-induced skin reactions in mice, ketanserin inhibited an increase of capillary permeability caused by each mediator. Cyproheptadine, at doses of 0.1 and 0.5 mg/kg, inhibits 48 hr and 1.5 hr homologous passive cutaneous anaphylaxis and histamine-induced capillary permeability increase in mice ear. The inhibitory activity of cyproheptadine on these reactions is more potent than that of ketanserin. However, ketanserin showed a more potent inhibition than cyproheptadine for serotonin-induced capillary permeability. In rat passive peritoneal anaphylaxis, ketanserin had little effect on the release of histamine from peritoneal mast cells. Ketanserin inhibited an antigen-induced contraction of the sensitized guinea-pig trachea at an early period (within 5 min after treatment with antigen) but not at a late period (between 5 to 15 min). Cyproheptadine had little effect on this antigen-induced contraction of sensitized guinea-pig trachea. Moreover, ketanserin inhibited both histamine- and serotonin-induced contractions of the guinea-pig trachea, but not the contraction caused by carbachol and LTC4. When Forssman antibody was injected into the guinea-pigs, a biphasic increase of airway resistance was observed. Ketanserin inhibited an increase of airway resistance at late phases. These results suggest that ketanserin inhibited some anaphylactic reactions in mice and guinea-pigs probably due to the antagonistic action of histamine and serotonin.