Preventive effect of the thromboxane A2 receptor antagonist S‐1452 (d‐s‐145 Ca) on arachidonate‐induced sudden death and cerebral infarction in rabbits

The thromboxane A2 (TXA2) receptor antagonist S‐1452, d‐S‐145 Ca, calcium 5(Z)‐1R,2S,3S,4S‐7‐[3‐phenylsulfonylaminobicyclo[2.2.1]hept‐2‐yl]‐5‐heptenoate dihydrate, prevented sudden death induced by arachidonate or U46619 in rabbits when given in a dose range between 0.1 mg/kg and 1 mg/kg, p.o. OKY‐046 and aspirin were also effective in this thromboembolism model, but 10 to 30 times larger doses were needed. Orally administered S‐1452 successfully prevented the incidence of cerebral infarction in the rabbit, which was elicited by infusion of 10 mg/ml sodium arachidonate at a rate of 0.1 ml/min for 30 min via a left internal carotid artery. Significant reduction of the infarction grade was observed in dosing above 3 mg/kg of this compound 1 to 4 h before the arachidonate infusion. OKY‐046 was effective similarly, but less active than S‐1452 (the minimum effective dose: 10 mg/kg). Ticlopidine and aspirin were entirely inactive in this model even after much larger doses. S‐1452 is a useful compound for prevention of TXA2‐mediated thrombosis in the brain.