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 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.
Petrusewicz
J
J
Faculty of Pharmacy, Medical Academy of Gdańsk, Poland.
Turowski
M
M
Foks
H
H
Pilarski
B
B
Kaliszan
R
R
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D020910:Ketorolac; D008297:Male; D051379:Mice; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011655:Pulmonary Embolism / Q000188:drug therapy; D011719:Pyrazines / Q000494:pharmacology*; D014046:Tolmetin / Q000031:analogs & derivatives / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D011719:Pyrazines; D000244:Adenosine Diphosphate; D003094:Collagen; D014046:Tolmetin; D007213:Indomethacin; D004837:Epinephrine; D020910:Ketorolac