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在川穹嗪(TMP)甲基上设计同位素开关(6D-TMP,12D-TMP),以试图减慢TMP氧化代谢,增强药效.对比研究TMP、6D-TMP、12D-TMP等对~(131)I、~(125)Ⅰ-双标记静脉血栓增长模型及血小板聚集的影响.结果表明6D-TMP、12D-TMP体内、体外抗血栓作用均大于TMP;血小板聚集实验表明,随着TMP、6D-TMP、12D-TMP给药剂量增加,三药在一定剂量范围均得良好量效关系,以其IC_(50).估算,12D-TMP与6D-TMP抑制血小板聚集作用强度分别约为TMP的2.67倍及1.27倍.大鼠体内实验亦表明,三药对ADP诱导的血小板聚集有抑制作用,12D-TMP作用最显著.提示对川芎嗪进行结构改造前景广阔.
The isotope switch (6D-TMP, 12D-TMP) was designed on the methyl ester of tetramethylpyrazine (TMP) in order to try to slow down the oxidation metabolism of TMP and enhance the efficacy. Comparative study of TMP, 6D-TMP, 12D-TMP, etc. 131) Effects of I, 125I-D labeled thrombus growth model and platelet aggregation. The results showed that the antithrombotic effects of 6D-TMP and 12D-TMP in vivo and in vitro were all greater than TMP; platelet aggregation experiments showed that with TMP, The doses of 6D-TMP and 12D-TMP increased, and the three drugs had good dose-response relationship in a certain dose range. Based on their IC50 estimates, the 12D-TMP and 6D-TMP inhibit platelet aggregation intensities were about TMP respectively. 2.67-fold and 1.27-fold. The rat in vivo experiments also showed that the three drugs have an inhibitory effect on platelet aggregation induced by ADP, and 12D-TMP has the most significant effect. This suggests that the structural transformation of ligustrazine is promising.