Timmermans P B, Van Zwieten P A
Arch Int Pharmacodyn Ther. 1977 Aug;228(2):237-50.
The hypotensive effect of clonidine and 27 of its structurally related imidazolidines, which differ in substitution in the aromatic moiety, was determined following intravenous application to pentobarbital-anaesthetized, normotensive rats. The decrease in cardiac frequency was measured at the moment of the maximal depressor effect. For all the compounds studied the same type of mechanism regarding their cardiovascular action is involved. Both the hypotensive and bradycardic effects were quantified by means of equipotent doses, calculated from dose-response characteristics constructed for each derivative. A wide range of bradycardic and hypotensive activities (greater than 4 logarithmic units) is covered by this selection of clonidine-like drugs. Moreover, a linear relationship is found between the hypotensive and bradycardic activities within the present series of compounds. The influence of structural modifications in the aromatic portion of the imidazolidines on hypotensive activity is described and discussed with respect to the structure-activity relationship (SAR) in centrally acting hypotensive imidazolidines.
在戊巴比妥麻醉的正常血压大鼠静脉注射后，测定了可乐定及其27种结构相关的咪唑烷类化合物的降压作用，这些化合物在芳香部分的取代有所不同。在最大降压效应出现时测量心率下降情况。对于所有研究的化合物，其心血管作用涉及相同类型的机制。降压和心动过缓效应均通过等效剂量进行量化，等效剂量是根据为每种衍生物构建的剂量-反应特性计算得出的。这种可乐定样药物的选择涵盖了广泛的心动过缓和降压活性（大于4个对数单位）。此外，在本系列化合物中，降压和心动过缓活性之间存在线性关系。就中枢性降压咪唑烷类化合物的构效关系（SAR）而言，描述并讨论了咪唑烷类化合物芳香部分的结构修饰对降压活性的影响。
