苯乙胺类新化合物抗前列腺增生作用研究

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (7): 726-735.

苯乙胺类新化合物抗前列腺增生作用研究

王荣荣¹, 江振洲^1,2, 习保民⁴, 王涛^1,3, 刘晶¹, 梁忠良¹, 张陆勇^1,2

¹中国药科大学江苏省新药筛选中心, ²药物质量与安全预警教育部重点实验室(中国药科大学),³江苏省药效研究与评价服务中心, 南京210009, 江苏;
⁴南方医科大学药学院药物化学系, 广州510515, 广东

收稿日期:2009-03-28 修回日期:2009-05-06 出版日期:2009-07-26 发布日期:2020-10-30
通讯作者: 张陆勇, 男, 教授, 博士生导师, 研究方向:分子药理学与毒理学、中药毒理学。Tel:025-85391056 　E-mail:lyzhang@cpu.edu.cn
作者简介:王荣荣, 女, 硕士, 研究方向:药理学。Tel:15896406172 　E-mail:bhlilin@126.com
基金资助:
国家自然科学基金资助(30690776)

Study on phenylethylamines new compounds against benign prostatic hyperplasia

WANG Rong-rong¹, JIANG Zhen-zhou^1,2, XI Bao-min⁴, WANG Tao^1,3, LIU Jing¹, LIANG Zhongliang¹, ZHANG Lu-yong^1,2

¹Jiangsu Center for Drug Screening, China Pharmaceutical University, ²Key Laboratory of Drug Quality Control and Pharmacovigilance(China Pharmaceutical University), Ministry of Education, ³Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, Jiangsu, China;
⁴Reseach Division of Pharmacochemistry, Southern Medical University, Guangzhou 510515, Guangdong, China

Received:2009-03-28 Revised:2009-05-06 Online:2009-07-26 Published:2020-10-30

摘要/Abstract

摘要： 目的:探讨具有α₁-肾上腺素受体(α₁-AR)拮抗作用的XBM 系列苯乙胺类新化合物的体外生物活性及体内药效作用。方法:SD 大鼠离体肛尾肌等张力试验, 观察XBM 系列新化合物的拮抗作用;流式细胞术检测XBM-21 的α₁-AR 亚型选择性;采用大鼠前列腺增生模型, 观察XBM-21 的抗前列腺增生作用。结果:大部分XBM 系列新化合物具有α₁-AR 拮抗作用, XBM-21 的pA2 值为8.42。钙流筛选测得XBM-21 在α₁A-AR、α₁B-AR和α₁D-AR 上的IC₅₀ 值分别为71.5 nmol/L、1.03 μmol/L、65 nmol/L, 且XBM-21 能明显改善大鼠前列腺增生模型的干湿重指数。结论:新化合物XBM-21 具有明显的α₁-AR 拮抗作用, 且亚型选择性较强, 提示该新化合物对良性前列腺增生所引起的症状将有较好的改善作用。

关键词: 良性前列腺增生, 离体肛尾肌, α₁-肾上腺素受体, 钙流筛选模型

Abstract: AIM: To study the bioactivities in vitro and the pharmacodynamic action in vivo of XBM series phenylethylamines as α₁-adrenocepter antagonist on benign prostatic hyperplasia.METHODS: The antagonism of XBMs on isolated SD rat anococcygeus musle was observed by isometric tension experiment.The adrenoceptor subtype selectivity of XBM-21 was identified by flow cytometry, and the effect of XBM-21 on benign prostatic hyperplasia model rats was also identified. RESULTS: Most of the XBM new compounds have antagonism on α₁-AR, the pA2 of XBM-21 was 8.42. The IC₅₀ of XBM-21 on α₁A-AR, α₁B-AR and α₁D-AR were 71.5 nmol/L, 1.03 μmol/L and 65 nmol/L, respectively.XBM-21 could obviously improve the dry and humid weight index of hyperplasia of prostate gland model rats.CONCLUSION: XBM-21 has siginificant antagonism on blocking α₁-adrenoceptor, it has good selectivities on α₁A-AR and α₁D-AR, which indicateed the new compound could better improve the symptom induced by benign prostatic hyperplasia.

Key words: benign prostatic hyperplasia (BPH), isolated rat anococcygeus musle, α₁-adrenoceptor antagonist, calcium influx screening essay

中图分类号:

R965.2

王荣荣, 江振洲, 习保民, 王涛, 刘晶, 梁忠良, 张陆勇. 苯乙胺类新化合物抗前列腺增生作用研究[J]. 中国临床药理学与治疗学, 2009, 14(7): 726-735.

WANG Rong-rong, JIANG Zhen-zhou, XI Bao-min, WANG Tao, LIU Jing, LIANG Zhongliang, ZHANG Lu-yong. Study on phenylethylamines new compounds against benign prostatic hyperplasia[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(7): 726-735.

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