COMPARATIVE-STUDIES OF ANTIPLATELET ACTIVITY OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS AND NEW PYRAZINE CH AND NH ACIDS

Nine known nonsteroidal antiinflammatory drugs (NSAID) and three new p yrazine derivatives possessing an active methylene moiety (pyrazine CH /NH-acids) were tested with regards to their in vitro and in vivo anti platelet activity. Concentrations of the agent were determined which c aused 25% and 50% inhibition of aggregation of human blood platelets i nduced by fixed concentrations of ADP, collagen and epinephrine. The i n vivo test consisted in determination of percent protection of mice f rom pulmonary microembolism caused by injection of a mixture of collag en and epinephrine. The in vitro antiaggregatory activity of the colla gen-induced aggregation CH/NH-acids appeared highly potent antithrombo tic agents in vivo. Activity of NSAID expressed as percent protection against lung thromboembolism in the mouse was demonstrated to depend q uantitatively on acid properties of the agents. The new chemical class of pharmacologically active agents, pyrazine CH/NH-acids, offers an o riginal pharmacophore which is distinctive from the carboxylic or enol ic functionalities typical for the established NSAID, and as such, may be devoid of some disadvantages of known antiplatelet drugs.