Fundamental Studies on Anti-allergy Drug, Especially from the View Point of Anti-serotonin Activity

Abstract

It is recognized that antihistaminics are not uniformaly effective in any allergic disorder and that some diseases of allergic origin are quite resistant to therapy. The failure of the antihistaminics in such situations has been attributed to the formation or liberation of substances other than histamine which either support or produce effects similar to the latter and which are not influenced by antihistaminics. A substance which is receiving increasing attention as a possible important entity in diseases of hypersensitivity is serotonin. Comparative studies of Diphenylpyraline (Hystamin), Cyproheptadine and LSD (lysergic acid diethylamide) were carried out. The activities related to anti-allergy were investigated. The results obtained were as follows; 1) In the protective activities of the drugs against edema produced by local injection of serotonin or egg-white in rats, Cyproheptadine was found to be so effective to edema produced by serotonin but Diphenylpyraline was also found to be comparatively effective. 2) It was shown that the pretreatment of Cyproheptadine or LSD is so protective against the lethal effect of serotonin in B. pertussis treated mice and Diphenylpyraline have slight effective activity. 3) It was shown that the pretreatment of Diphenylpyraline completely protected against the death by anaphylactic shock and Cyproheptadine or LSD have also protective effect against anaphylactic shock. 4) In vitro activities of the anti-allergy drugs against the contraction of the isolated guinea pig intestine induced by histamine, acetylcholine, serotonin, barium chloride and anaphylaxis were studied. The results show that Cyproheptadine is superior in anti-serotonin activity than that of Diphenylpyraline and Diphenylpyraline is superior in antihistamine and anti-barium chloride activity than that of Cyproheptadine.