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新型抗痴呆药物吲哚[2',3':3,4]吡啶并[2,1 - b]喹唑啉鎓 - 5,7,8,13 - 四氢 - 14 - 甲基 - 5 - 氧代氯化物的一般药理学

General pharmacology of indole [2',3':3,4]pyrido[2,1-b]quinazolinium- 5,7,8,13-tetrahydro-14-methyl-5-oxo-chloride, a new anti-dementia agent.

作者信息

Park Cheol Hyoung, Choi Se Hoon, Kim Chan-Hyung, Seo Ji-Heui, Koo Ja Wook, Rah Jong-Cheol, Kim Hye-Sun, Jeong Sung-Jin, Joo Wan-Seok, Lee Young-Jae, Kim Yong Sik, Kim Myung-Suk, Suh Yoo-Hun

机构信息

Department of Pharmacology, College of Medicine, National Creative Research Initiative Centre for Alzheimer's Dementia, Neuroscience Research Institute, MRC, Seoul National University, Seoul, Korea.

出版信息

Arzneimittelforschung. 2003;53(6):393-401. doi: 10.1055/s-0031-1297126.

Abstract

The general pharmacological properties of indolo[2',3':3,4]pyrido[2,1-b]quinazolinium-5,7,8,13-tetrahydro-14- methyl-5-oxo-chloride (dehydroevodiamine-HCl, DHED, CAS 67909-49-3), a new potential anti-dementia agent, were studied to investigate side effects using various experimental animals. Both oral and intraperitoneal administration of DHED had no effects on the central nervous system except that they showed an analgesic activity. DHED had no significant effect on heart rate, blood pressure and coronary flow in isolated rat hearts. DHED had negligible effects on the autonomic nervous system and smooth muscle in isolated rat ileum, rat vas deferens and rat aorta. DHED did not influence the gastrointestinal system except that it inhibited the intestinal travel of a charcoal meal in mice. Neither blood coagulation mechanism nor liver function was affected by DHED. Therefore, it is concluded from these general pharmacological studies that DHED does not induce any serious side effects at the dose levels showing anticholinesterase and memory enhancing activities in the experimental animals.

摘要

新型潜在抗痴呆药物吲哚并[2',3':3,4]吡啶并[2,1 - b]喹唑啉鎓 - 5,7,8,13 - 四氢 - 14 - 甲基 - 5 - 氧代氯化物(盐酸去氢吴茱萸碱,DHED,CAS 67909 - 49 - 3)的一般药理学特性,通过使用各种实验动物进行研究以调查其副作用。口服和腹腔注射DHED对中枢神经系统均无影响,仅表现出镇痛活性。DHED对离体大鼠心脏的心率、血压和冠脉流量无显著影响。DHED对离体大鼠回肠、大鼠输精管和大鼠主动脉的自主神经系统和平滑肌影响可忽略不计。DHED除抑制小鼠肠道内炭末推进外,对胃肠系统无影响。DHED对血液凝固机制和肝功能均无影响。因此,从这些一般药理学研究得出结论,在实验动物中显示抗胆碱酯酶和增强记忆活性的剂量水平下,DHED不会引起任何严重副作用。

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