多沙唑嗪及其手性对映体对离体兔血管α1受体的拮抗特性  

α1-Adrenoceptor antagonist profile of doxazosin and its enantiomers in isolated rabbit blood vessels

作　　者：牛长群[1] 赵丁[2] 贾湘曼[2] 任雷鸣[2] 

机构地区：[1]河北医科大学药学院药理学研究室,河北,石家庄,050017,华北制药集团新药研究开发中心,河北,石家庄,050015 [2]河北医科大学药学院药理学研究室,河北,石家庄,050017

出　　处：《中国药理学与毒理学杂志》2003年第5期354-359,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：教育部博士后科学基金

摘　　要：目的分析α1肾上腺素受体阻断药多沙唑嗪手性对映体对兔胸主动脉和颈总动脉的选择性作用,以探讨作为良性前列腺增生症治疗药物的可能性.方法测定去甲肾上腺素(NE)诱发兔离体胸主动脉和颈总动脉收缩反应,并采用Schild作图法计算rac-多沙唑嗪、R-多沙唑嗪和S-多沙唑嗪的pA2值.结果在兔胸主动脉和颈总动脉,0.03, 0.1和0.3 μmol*L-1的rac-多沙唑嗪、R-多沙唑嗪和S-多沙唑嗪均使NE诱发的血管收缩反应量效曲线平行右移,Emax不变;由Schild作图法计算得到的多沙唑嗪及其手性对映体的斜率值,经统计学分析符合竞争性拮抗.3种拮抗剂pA2值的强度顺序为:R-多沙唑嗪>rac-多沙唑嗪>S-多沙唑嗪.结论与多沙唑嗪及其手性对映体对人前列腺组织作用的报道结果不同,S-多沙唑嗪对兔胸主动脉和颈总动脉α1肾上腺素受体拮抗作用的选择性显著低于rac-多沙唑嗪和R-多沙唑嗪.AIM: To investigate the different selectivity of α 1-adreno ce ptor antagonist R-doxazosin and S-doxazosin in the rab bit thoracic aorta and carotid artery as potentially therapeutic agent for benig n prostatic hyperplasia. METHODS Isometric contractile responses to nor- epinephrine(NE) in the rabbit thoracic aorta and carotid artery were obser ved, and the pA 2 values of doxazosin and its enantiomers were calculated from the Schild plots. RESULTS rac-Doxazosin, R-doxazosin or S-doxazosin at 0.03, 0.1 and 0.3 μmol·L -1 produced paral lel shifts to the right of the concentration-response curves for NE without sig nificant decrease in the E max values in the rabbit thoracic aorta and caro tid artery. The slope of the Schild plot for rac-, R- or S-doxazosin was not significantly different from unity, indicating that thr ee agents competitively inhibited the concentration-response curves for NE. Th e rank order of the α 1-adrenoceptor antagonist pA 2 was R-doxa zosin>rac-doxazosin>S-doxazosin in the rabbit thoracic aorta and c arotid artery. CONCLUSION To be contrary to the previously report ed res ults in the human prostate, the selectivity of S-doxazosin against α 1-adrenoceptor is significantly lower than that of rac-doxazosin and R-doxazosin in the rabbit thoracic aorta and carotid artery.

关 键 词：多沙唑嗪 手性对映体 肾上腺素 Α1受体 主动脉 胸 颈动脉 兔 拮抗特性 

分 类 号：R96[医药卫生—药理学]