Antithrombotic activity of p-aminobenzoic acid upon experimental thrombosis

It was shown for the first time that p-aminobenzoic acid (PABA), in additio n to the previously described fibrinolytic activity, exerts the properties of a direct anticoagulant both in vitro and in vivo. PABA not only displays antithrombin activity, but also inhibits activated factor X and, upon intr avenous injection to rats and rabbits, shows the antithrombotic effect. The most pronounced antithrombotic affect was observed at a dose of 1.5 mg/kg. PABA at 0.5 mg/kg has insignificant efficacy and at 3 mg/kg, a high effica cy, but induces hemolysis of erythrocytes in about a half of cases. Equally efficient antithrombotic activity of blood plasma of rats was noted after intravenous injection of low molecular weight heparin "Fraxiparin" at 40 an ti-Xa U/kg and PABA at 25 anti-Xa U/kg (1.5 mg/kg). Unlike "Fraxiparin". wh ich exerts on immediate effect, the effect of PABA was expressed within 1.5 to 5 h after injection with a peak of antithrombotic activity at 3 h (whic h correlates with anti-IIa and anti-Xa activities of plasma) and terminated by 5 h after injection. For PABA, the ratio of anti-Xa to anti-IIa activit ies (an important parameter, which determines the antithrombotic potential of drugs) equals 2.4. PABA at 0.5 or 1.5 mg/kg did not affect the number of thrombocytes, while at 3 mg/kg, it decreased the number of thrombocytes by 20%. Thus PABA at 1.5 mg/kg, which has a high anticoagulant activity and d oes not cause side effects, is most interesting for further studies.