Vermylen J, Defreyn G, Carreras L O, Machin S J, Van Schaeren J, Verstraete M
Lancet. 1981 May 16;1(8229):1073-5. doi: 10.1016/s0140-6736(81)92241-8.
The imidazole derivative UK-37 248, a thromboxane synthetase inhibitor, reduces the in-vitro formation of thromboxane B2 and hydroxyheptadecatrienoic acid by washed platelets, and this is compensated for by an increased production of prostaglandins E2 and F2 alpha; arachidonic acid challenged platelets pretreated with UK-37 248 also stimulate the production of prostacyclin by aspirin pretreated cultured endothelial cells. In a double-blind placebo controlled study to examine the in vivo properties of UK-37 248, human volunteers ingested 200 mg of the compound. Their serum thromboxane B2 levels dropped and their plasma 6-keto-prostaglandin F1 alpha values rose. Arachidonic acid induced platelet aggregation was completely inhibited whereas that elicited by adenosine-5'-diphosphate was unaffected. By reducing formation of pro-aggregatory tromboxane A2 and increasing production of anti-aggregatory prostacyclin, thromboxane synthetase inhibitors may be better than aspirin as antithrombotic agents.
咪唑衍生物UK - 37 248是一种血栓素合成酶抑制剂，它可减少洗涤血小板在体外形成血栓素B2和羟基十七碳三烯酸，而这会因前列腺素E2和F2α生成增加而得到补偿；用UK - 37 248预处理的花生四烯酸刺激的血小板也会刺激经阿司匹林预处理的培养内皮细胞生成前列环素。在一项双盲安慰剂对照研究中，为检测UK - 37 248的体内特性，人类志愿者摄入了200毫克该化合物。他们的血清血栓素B2水平下降，血浆6 - 酮 - 前列腺素F1α值上升。花生四烯酸诱导的血小板聚集被完全抑制，而由腺苷 - 5'-二磷酸引发的血小板聚集则未受影响。通过减少促聚集血栓素A2的形成并增加抗聚集前列环素的生成，血栓素合成酶抑制剂作为抗血栓药物可能比阿司匹林更有效。
