兔离体主动脉、心房和空肠标本中紫杉醇与维拉帕米心脏选择性的比较测定

Tekol Y, Göğüsten B

Department of Pharmacology, Medical Faculty, Erciyes University, Kayseri, Turkey.

Arzneimittelforschung. 1999 Aug;49(8):673-8. doi: 10.1055/s-0031-1300481.

The calcium channel antagonistic effect of taxine (CAS 12607-93-1) (active principle of leaves of English yew; Taxus baccata L.) was investigated in isolated aorta of rabbit, and its organ selectivity was determined and compared with that of verapamil (CAS 52-53-9) in isolated aorta, atrium and jejunum preparations of rabbits. Taxine (10(-6)-10(-4) g/ml) inhibited concentration-dependently the Ca(2+)-induced contractions of the aorta depolarized by 60 mmol/l K+ in Ca2+ free media. Both taxine (3 x 10(-7)-10(-4) g/ml) and verapamil (10(-10)-10(-7) g/ml) relaxed the aorta, which was precontracted by 60 mmol/l K+, in a concentration-dependent manner. The IC50 of taxine was 4.78 x 10(-6) and that of verapamil 2.45 x 10(-9) g/ml. Similar effects of taxine were observed in the endothelium-denuded aortic strips. Taxine (3 x 10(-8)-10(-5) g/ml) and verapamil (10(-10)-10(-6) g/ml) produced concentration-dependent negative inotropic and chronotropic effects on isolated atrium preparations. The IC50 values of taxine were 3.63 x 10(-7), and 5.75 x 10(-7) g/ml and those of verapamil 2.69 x 10(-9) and 3.71 x 10(-8) g/ml for contraction and rate, respectively. Taxine and verapamil reduced the amplitude of peristaltic movements of the jejunum. The IC50 values were 1.86 x 10(-5) g/ml for taxine and 3.80 x 10(-8) g/ml for verapamil. From these data it was concluded that taxine has calcium channel antagonistic activity. It was found that taxine was about 13 times more selective for the heart than the vessel and 51 times more selective for the heart than the intestine with respect to inotropic effects, and 8 times more selective for the heart than the vessel, and 32 times more selective for the heart than the intestine in regard to chronotropic effects. When compared with relative selectivity between heart and vessel, taxine is about 14 and 126 times more selective for the heart than verapamil with respect to inotropic and chronotropic effects, and taxine is about 4 and 32 times more selective for the heart than verapamil when compared with relative selectivity on the intestine in regard to inotropic and chronotropic effects, respectively.

研究了紫杉碱（CAS 12607-93-1）（欧洲红豆杉叶的活性成分；欧洲红豆杉）对兔离体主动脉的钙通道拮抗作用，并测定了其器官选择性，并与维拉帕米（CAS 52-53-9）在兔离体主动脉、心房和空肠标本中的作用进行比较。紫杉碱（10⁻⁶ - 10⁻⁴ g/ml）在无钙培养基中浓度依赖性地抑制60 mmol/l K⁺使主动脉去极化后Ca²⁺诱导的收缩。紫杉碱（3×10⁻⁷ - 10⁻⁴ g/ml）和维拉帕米（10⁻¹⁰ - 10⁻⁷ g/ml）均以浓度依赖性方式使60 mmol/l K⁺预收缩的主动脉舒张。紫杉碱的IC50为4.78×10⁻⁶ g/ml，维拉帕米的IC50为2.45×10⁻⁹ g/ml。在去内皮的主动脉条上观察到紫杉碱的类似作用。紫杉碱（3×10⁻⁸ - 10⁻⁵ g/ml）和维拉帕米（10⁻¹⁰ - 10⁻⁶ g/ml）对离体心房标本产生浓度依赖性的负性肌力和负性频率作用。紫杉碱对收缩和频率的IC50值分别为3.63×10⁻⁷和5.75×10⁻⁷ g/ml，维拉帕米分别为2.69×10⁻⁹和3.71×10⁻⁸ g/ml。紫杉碱和维拉帕米均降低空肠蠕动幅度。紫杉碱的IC50值为1.86×10⁻⁵ g/ml，维拉帕米的IC50值为3.80×10⁻⁸ g/ml。从这些数据得出结论，紫杉碱具有钙通道拮抗活性。发现就正性肌力作用而言，紫杉碱对心脏的选择性比对血管高约13倍，对心脏的选择性比对肠道高51倍；就负性频率作用而言，紫杉碱对心脏的选择性比对血管高8倍，对心脏的选择性比对肠道高32倍。与心脏和血管之间的相对选择性相比时，就正性肌力和负性频率作用而言，紫杉碱对心脏的选择性比维拉帕米高约14倍和126倍；就正性肌力和负性频率作用而言，与在肠道上的相对选择性相比时，紫杉碱对心脏的选择性比维拉帕米高约4倍和32倍。