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| 1,2,5,6-4H-1-烷基-3-取代吡啶类新衍生物对血管内皮细胞功能的调节作用及其构效关系 | |
| 引用本文： | 石翠格,胡国强,胡刚,黄文龙,汪海. 1,2,5,6-4H-1-烷基-3-取代吡啶类新衍生物对血管内皮细胞功能的调节作用及其构效关系[J]. 中国临床药理学与治疗学, 2003, 8(6): 613-617 |
| 作者姓名： | 石翠格 胡国强 胡刚 黄文龙 汪海 |
| 作者单位： | 1. 南京医科大学药理学与神经生物学系,南京,210029,江苏 2. 中国药科大学新药研究中心,南京,210009,江苏 3. 军事医学科学院毒物药物研究所,北京,100850 |
| 基金项目： | 国家重点基础研究发展规划项目(№GT1998051112);北京赛德维康医药研究院新药研究基金项目(№1999001) |
| 摘 要： | 目的：以槟榔碱为结构母核，设计合成1，2，5，6-4H-1-烷基-3-取代吡啶类新衍生物，分析其对血管内皮细胞功能的影响。方法：采用离体大鼠主动脉环和离体豚鼠回肠收缩实验，分别观察新结构化合物对血管和回肠平滑肌张力的影响；并进一步观察一氧化氮合酶抑制剂L-NAME、环氧酶抑制剂吲哚美辛、M受体亚型非选择性激动剂毛果芸香碱和M受体亚型非选择性拮抗剂阿托品对新结构化合物诱发的血管舒张反应的影响。结果：从100个新化合物中发现4个有舒血管反应，但不激活M受体的化合物，分别是HH91、HH95、HH98、HH103。新化合物HH103诱发的内皮依赖性舒血管反应可被L-NAME所拮抗，但不被吲哚美辛、阿托品和毛果芸香碱拮抗。结论：新化合物可诱发内皮依赖性舒张反应并具有特定构效关系；HH103通过促进内皮细胞释放NO发挥其效应；但其作用特征又与乙酰胆碱不同。 |
| 关 键 词： | 药理学 血管内皮细胞 M受体 乙酰胆碱 槟榔碱 构效关系 |
| 文章编号： | 1009-2501(2003)06-0613-05 |
| 修稿时间： | 2003-04-21 |
Effects of alkyl-1,2,5,6-tetrahydro-3-substituted pyridine derivatives on the functions of vascular endothelial cells and its structure-activity relationship |
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| SHI Cui-Ge ,HU Guo-Qiang ,HU Gang ,HUANG Wen-Long ,WANG Hai Institute of Pharmacology and Toxicology,Academy of Military Medical Science,B eijing ,China. Effects of alkyl-1,2,5,6-tetrahydro-3-substituted pyridine derivatives on the functions of vascular endothelial cells and its structure-activity relationship[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2003, 8(6): 613-617 | |
| Authors: | SHI Cui-Ge HU Guo-Qiang HU Gang HUANG Wen-Long WANG Hai Institute of Pharmacology Toxicology Academy of Military Medical Science B eijing China |
| Affiliation: | SHI Cui-Ge 1,HU Guo-Qiang 2,HU Gang 1,HUANG Wen-Long 2,WANG Hai Institute of Pharmacology and Toxicology,Academy of Military Medical Science,B eijing 100850,China, 1 Department of Pharmacology and Neurobiology,Nanjing M edical University,Nanjing 210029,Jiangsu,China, 2 Drug Research and Develop ment Center,China Pharmaceutical University,Nanjing,210009,Jiangsu,China |
| Abstract: | AIM: To observe the influence of alkyl-1,2,5,6-tetrahydro -3-substituted pyridine analogy compounds on the function of endothelial cells . METHODS: The effects of L-NAME, indomethacin, pil ocarpine and atropine on the novel compounds were observed using the isolated ra t aorta and guinea pig ileum model. RESULTS: Among 100 compounds , 4 leading compounds were found, which included HH91, HH95, HH98, and HH103. Th e endothelium-dependent relaxation mediated by HH103 could be blocked by L-NAME, but not by indomethacin, pilocarpine and atropine. CONCLU SION: The novel compounds can mediate endothelium-dependent relaxation and had unique structure-activity relationship. The function of endothelium-d ependent relaxation mediated by HH103 is performed by promoting the secrete of NO, but different from that of ACh. |
| Keywords: | pharmacology en dothelial cells muscarinic receptor acetylcholine arecoline structure-activ ity relationship |
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