十二种莨菪碱类衍生物药理作用的比较

本研究用放射配基结合法测定了十二种莨菪碱类衍生物对豚鼠回肠纵长肌M胆碱受体的亲和力,并测定了其油水分布系数和对动物记忆获得的影响。结果表明,大部分衍生物季铵盐化后可降低与受体的亲和力和油水分布系数,但是托品酸α位碳原子上带有一个羟基的季铵盐如8610等,其与受体的亲和力分别比东莨菪碱和正丁基东莨菪碱强10倍和100倍,而油水分布系数却比东莨菪碱和阿托品小。十二种莨菪碱类衍生物阻抑小鼠记忆获得所需剂量比东莨菪碱大2.5到5倍不等。

COMPARATIVE STUDY ON THE PHARMACOLOGICAL EFFECTS OF SOME SCOPOLIA ALKALOID DERIVATIVES

The effects of some scopolia alkaloid derivatives on M-cholinergic receptors of longitudinal muscle from guinea pig ileum were studied. Measurements of the oil/water partition coefficients and amnestie actions of these compounds were also made. Results showed that quaternization of most compounds decreased both the affinities to M-receptor and the oil/water partition coefficient. But, compounds with a hydroxyl group in the α-carbon atom of the carboxylic acid of the ester chain, such as 8610 showed potent displacement activities which were 10 and 100 times higher than those of scopolamine and N-butylscopolamine, respectively. However, the oil/water partition coefficients were lower than those of atropine and scopolamine. Twelve derivatives of the scopolia alkaloid were shown to impair memory acquisition in one trial passive avoidence responses in mice and their amnestic efficacies were 2.5～5 times lower than that of scopolamine.