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

✍ Scribed by Hirokuni Jyoy; Atsushi Kurosawa

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 506 KB
• Volume: 30
• Category: Article
• ISSN: 0272-4391
• DOI: 10.1002/ddr.430300205

✦ Synopsis

The thromboxane A, (TXA,) receptor antagonist S-1452, d-S-145 Ca, calcium 5(Z)-1R,2S,3S, 4S-7-[3-phenylsulfonylaminobicyclo[2.2.llhept-2-yll-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.0. 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 m h i n 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. 5-1452 IS a useful compound for prevention of TXA,mediated thrombosis in the brain.