harmacological Effects of OKY-1581 of Thromboxane A₂ Synthetase Inhibito

Abstract

We studied the pharmacological and biochemical effects of OKY-1581 which was a specific inhibitor of thromboxane synthetase. The following results were obtained.
IC₅₀ value for rabbit platelet thromboxane synthetase was 3X10-9 M. OKY-1581 inhibited the rabbit platelet aggregation induced by arachidonic acid (IC₅₀=5.8X10-7M). Rabbit sudden death induced by arachidonic acid (4mg/kg, iv) was protected by oral administration (30mg/kg). Inhibition of arachidonic acid induced vascular contraction was also observed by intravenous administration (0.01mg/kg). Ex vivo experiment using monkeys showed that OKY-1581 admini-stered orally at a dose of 0.5mg/Icg inhibited the TXB2 production in serum over 7 hours.
From these results, OKY-1581 could be useful for diseases such as angina, myocardial infarction and cerebral infarction in which the thromboxane synthesis was enhanced.