文章基本信息

标题：Characteristic Subcellular Distribution, in Brain, Heart and Lung, of Biperiden, Trihexyphenidyl, and (-)-Quinuclidinyl Benzylate in Rats
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作者：Junko ISHIZAKI ; Koichi YOKOGAWA ; Emi NAKASHIMA 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1998
卷号：21
期号：1
页码：67-71
DOI：10.1248/bpb.21.67
出版社：The Pharmaceutical Society of Japan
摘要：The subcellular distribution of biperiden (BP), trihexyphenidyl (TP) and (-)-quinuclidinyl benzylate (QNB) in brain, heart and lung following high dose (3.2mg/kg) i.v. administration was investigated in rats. The subcellular distribution of BP or TP used clinically conformed with that of QNB, a typical potent central muscarinic antagonist. The concentration-time courses of the brain subcellular fractions for these drugs were of two types which decreased slowly and in parallel to the plasma concentration. The subcellular distribution in the brain and heart was dependent on the protein amount of each fraction. The percent post-nuclear fraction (P₂) of the total concentration in the lung was characteristically about 3-5 times larger than that in the heart. It was elucidated that the distribution in the lung differs from that in the brain and heart, with high affinity which is not dependent on the protein amount in the P₂ fraction containing lysosomes. On the other hand, at a low dose (650ng/kg) of ³H-QNB, each fraction as a percentage of the total concentration in the brain increased in synaptic membrane and synaptic vesicles and decreased in nuclei and cytosol as compared with the high dose. These results show that although the tissue concentration-time courses of anticholinergic drugs appear to decrease simply in parallel to plasma concentration, the subcellular distribution exhibits a variety of patterns among various tissues.
关键词：anticholinergic drug;subcellular distribution;lysosome;biperiden;trihexyphenidyl;quinuclidinyl benzylate