STUDIES ON ASPIRIN DERIVATIVES WITH VERY LITTLE SIDE EFFECT. IV.^<1)> INHIBITORY EFFECT OF ASPIRIN-ISOPROPYLANTIPYRINE (AIA) ON SEVERAL EXPERIMENTAL THROMBOSES

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The effect of a new aspirin derivative, aspirin-isopropylantipyrine (AIA), with potent platelet anti-aggregant activity, on several experimental thromboses was evaluated and compared with that of aspirin. AIA (50 mg./kg, s.c.) as well as aspirin (50 mg/kg, s.c.) significantly inhibited thrombus formation in extracorporeal shunt model of rats. AIA (50 mg/kg, s.c.) significantly shortened the duration of apnea and respiratory distress induced by a rapid injection of adenosine 5'-diphosphate in rats, while aspirin (50 mg/kg, s.c.) did not. Inhibitory effect of AIA (50 mg/kg, s.c.) on arachidonic acid-induced mortality in mice was less than that of aspirin (50 mg/kg, s.c.). AIA ang aspirin (10 mg/kg/d×10,s.c.) had no effect on laurate-induced arterial occlusive disease in rats. AIA (200 μM) showed weak and reversible inhibition of prostaglandin I_2 generation in isolated rat aorta strip, while aspirin (200 μM) showed irreversible inhibition. AIA (50 and 200 μM inhibited Ca^<2+>-, K^+-or norepinephrine-induced contraction on isolated rat aorta strip. AIA (200 μM) had no effect on malondialdehyde formation, cyclic AMP level and adenylate cyclase activity in rat plateless. AIA (100 μM) inhibited arachidonic acid-induced contraction on rat fundus strip by about 50%, while aspirin (100 μM) did not. These results strongly suggest that anti-thrombotic activity of AIA was originated at least from its anti-aggregant effect on platelets, differing from aspirin.
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STUDIES ON ASPIRIN DERIVATIVES WITH VERY LITTLE SIDE EFFECT. IV.^<1)> INHIBITORY EFFECT OF ASPIRIN-ISOPROPYLANTIPYRINE (AIA) ON SEVERAL EXPERIMENTAL THROMBOSES

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