Diazabicycloalkanesの研究(第1報)Octahydro-2H-pyrido[1,2-a]pyrazine誘導体ならびに類似化合物の薬理学的研究特に抗ヒスタミン作用について

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Antihistaminic and other pharmacological actions both in vitro and in vivo were evaluated on 18 compounds involving octahydro-2H-pyrido[1,2-a]pyrazine (I), decahydropyrido[1,2-d][1,4]diazepine (II), and decahydropyrido[1,2-a][1,4]diazepine (III) derivatives, and correlation between chemical structure and antihistaminic activity was investigated. Since it was found that the most effective gross structure and substituent was I and a benzhydryl grouping, respectively, 2-benzhydryloctahydro-2H-pyrido[1,2-a]pyrazine (I-2) was established as the most powerful agent among these compounds. This was demonstrated by the fact that I-2 exhibited a high antihistaminic potency both in vitro and in vivo, as well as a strong adsorbability to guinea pig ileum which was estimated to be equivalent to diphenhydramine (IV). Furthermore, I-2 gave a lower acute toxicity than IV or homochlorcyclizine and was more effective than IV not only in antiserotoninic and anticholinergic activities but also in anti-barium activity. A weak surface anesthetic effect of I-2 was also observed on the cornea of a guinea pig.
公益社団法人日本薬学会の論文
1972-11-25