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.
Nagai
H
H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Suda
H
H
Kitagaki
K
K
Goto
S
S
Miura
T
T
Koda
A
A
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001200:Ascaris / Q000276:immunology; D004205:Cromolyn Sodium / Q000494:pharmacology; D003533:Cyproheptadine / Q000494:pharmacology; D005260:Female; D005577:Forssman Antigen / Q000276:immunology; D006168:Guinea Pigs; D006633:Histamine Antagonists; D006636:Histamine Release / Q000187:drug effects; D006967:Hypersensitivity / Q000188:drug therapy*; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000037:antagonists & inhibitors; D012702:Serotonin Antagonists
D006633:Histamine Antagonists; D013189:SRS-A; D012702:Serotonin Antagonists; D003533:Cyproheptadine; D005577:Forssman Antigen; D007650:Ketanserin; D004205:Cromolyn Sodium