A new compound, azelastine, 4-(p-chlorobenzyl)-2-[N-methyl-perhydroazepinyl-(4)]-1-(2H) -phthalazinone hydrochloride, has recently been proved to be an effective antiallergy drug. It is quite different in its chemical structure from hitherto reported antiallergy drugs. In the present investigation, the inhibitory effects of azelastine against the immediate type allergic reactions in the guinea pig or the rat were studied in comparison with those of known antihistamine drugs, clemastine and chlorpheniramine. The results obtained were as follows:
1) The contraction of the small intestine isolated from the intact guinea pig or the rat by adding the histamine, bredykinin, serotonin, acetylcholine were remarkably inhibited by the pretreatment of azelastine.
2) The guinea pigs pretreated orally with a dose of 0.1 mg/kg of azelastine were completely protected from shock, resulting in death by a lethal dose of intravenous injection of histamine (1 mg). When the guinea pigs were pretreated with 1 mg/kg of azelastine 18 hours before the challenging injection of histamine, they were completely protected from shock death, and even if the pretreatment were done 24h before the challenging injection the survival rate of them was 80%.
3) The inhibitory effect of azelastine against the induction of heterologous PCA in the guinea pig and homologous PCA in the rat was rather potent in comparison with that of clemastine or chlorpheniramine.
4) Histamine release from the rat peritoneal mast cells by compound 48/80 or anti-rat IgE serum seemed to be slightly inhibited by the pretreatment with azelastine at the concentration of 10-8-10-6 M.
The results indicate that azelastine has a more potent antiallergic effect than such antihista-mine drugs as clemastine or chlorpheniramine.