Petrusewicz J, Turowski M, Foks H, Pilarski B, Kaliszan R
Faculty of Pharmacy, Medical Academy of Gdańsk, Poland.
Life Sci. 1995;56(9):667-77. doi: 10.1016/0024-3205(94)00500-r.
Nine known nonsteroidal antiinflammatory drugs (NSAID) and three new pyrazine derivatives possessing an active methylene moiety (pyrazine CH/NH-acids) were tested with regards to their in vitro and in vivo antiplatelet activity. Concentrations of the agents were determined which caused 25% and 50% inhibition of aggregation of human blood platelets induced by fixed concentrations of ADP, collagen and epinephrine. The in vivo test consisted in determination of percent protection of mice from pulmonary microembolism caused by injection of a mixture of collagen and epinephrine. The in vitro antiaggregatory activity of the agents studied was rather low, excepting the inhibition of the collagen-induced aggregation by ketoprofen. Several NSAID and two new pyrazine CH/NH-acids appeared highly potent antithrombotic agents in vivo. Activity of NSAID expressed as percent protection against lung thromboembolism in the mouse was demonstrated to depend quantitatively on acid properties of the agents. The new chemical class of pharmacologically active agents, pyrazine CH/NH-acids, offers an original pharmacophore which is distinctive from the carboxylic or enolic functionalities typical for the established NSAID, and as such, may be devoid of some disadvantages of known antiplatelet drugs.
对九种已知的非甾体抗炎药（NSAID）和三种具有活性亚甲基部分的新型吡嗪衍生物（吡嗪CH/NH-酸）进行了体外和体内抗血小板活性测试。测定了这些药物的浓度，其可导致由固定浓度的ADP、胶原蛋白和肾上腺素诱导的人血小板聚集抑制25%和50%。体内试验包括测定小鼠免受由注射胶原蛋白和肾上腺素混合物引起的肺微栓塞的保护百分比。除了酮洛芬对胶原蛋白诱导的聚集有抑制作用外，所研究药物的体外抗聚集活性相当低。几种NSAID和两种新型吡嗪CH/NH-酸在体内表现出高效的抗血栓形成剂作用。以小鼠肺血栓栓塞保护百分比表示的NSAID活性在定量上取决于药物的酸性性质。新型药理活性剂吡嗪CH/NH-酸提供了一种独特的药效基团，其不同于已确立的NSAID典型的羧基或烯醇官能团，因此可能没有已知抗血小板药物的一些缺点。
