Jancinová V, Májeková M, Nosál R, Petríková M
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Blood Coagul Fibrinolysis. 1996 Mar;7(2):191-3.
The effects of bromadryl, dithiaden, chloroquine and propranolol on thrombin-stimulated rat platelet aggregation (measured turbidimetrically) and thromboxane B2 generation (detected by an RIA method) were compared with four selected physico-chemical parameters of these drugs. Platelet aggregation was inhibited in the rank order of potency: bromadryl > dithiaden > propranolol > chloroquine, which corresponded with the decrease in the net charge of the terminal methyl-(or ethyl-) groups in the side chain and with the increase of the dipole moment of drug molecules. On the other hand, the rank order of potency in which the drugs tested inhibited thromboxane B2 formation (chloroquine > dithiaden > bromadryl > propranolol) correlated well with the decline in molar refractivity of the drugs. No relationship was found between inhibitory effects of drugs and their partition coefficients. The results presented indicate that inhibition of platelet functions might consist of several types of drug-cell interactions, depend on the structure and physico-chemical properties of the drugs and cannot be estimated simply on the basis of partition coefficients.
将溴马地尔、二硫氮卓、氯喹和普萘洛尔对凝血酶刺激的大鼠血小板聚集（用比浊法测定）和血栓素B2生成（用放射免疫分析法检测）的影响与这些药物的四个选定理化参数进行了比较。血小板聚集的抑制效力顺序为：溴马地尔＞二硫氮卓＞普萘洛尔＞氯喹，这与侧链末端甲基（或乙基）基团净电荷的减少以及药物分子偶极矩的增加相对应。另一方面，所测试药物抑制血栓素B2形成的效力顺序（氯喹＞二硫氮卓＞溴马地尔＞普萘洛尔）与药物摩尔折射度的下降密切相关。未发现药物的抑制作用与其分配系数之间存在关联。所呈现的结果表明，药物对血小板功能的抑制可能由几种类型的药物 - 细胞相互作用组成，取决于药物的结构和理化性质，不能仅根据分配系数来估计。
