[The pharmacological properties of a new anti-allergic agent, KP-136, in cutaneous models].
The pharmacological properties of KP-136 were studied using cutaneous reactions in rats and guinea pigs. KP-136 remarkably inhibited the passive cutaneous anaphylaxis (PCA) with intravenous and oral dosing. However, the inhibitory effect of KP-136 had an apparent species difference. Thus, KP-136 was more effective on rat PCA than that of guinea pig. In four rat cutaneous reactions produced by three allergic reactions and compound 48/80, KP-136 was remarkably effective on two homologous PCA induced by IgE and IgGa. The intravenous and oral doses for 50% inhibition on the PCA were 0.2 mg/kg to 0.4 mg/kg and 0.5 mg/kg to 0.9 mg/kg, respectively. KP-136 was scarcely effective on cutaneous reactions elicited by intradermal injection of histamine and serotonin which are main chemical mediators in rat homologous PCA. However, KP-136 blocked the degranulation of mast cells and decrease of histamine content in skin elicited by the PCA. In addition, KP-136 showed a potent inhibition on the immunological release of histamine from rat peritoneal exudate cells. The concentration for 50% inhibition on the histamine release was 5 ng/ml. These findings indicate that KP-136 is an oral potent inhibitor on PCA, and it acts by blocking the release of chemical mediator(s) from mast cells.
D000284:Administration, Oral; D000818:Animals; D002867:Chromones / Q000008:administration & dosage / Q000494:pharmacology*; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007275:Injections, Intravenous; D008407:Mast Cells / Q000187:drug effects; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000187:drug effects; D013045:Species Specificity; D013777:Tetrazoles
D002867:Chromones; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D013777:Tetrazoles; D007073:Immunoglobulin E; C053066:KP 136