Inhibition of thromboxane B2 formation of blood platelets by trapidil and other s-triazolo(l,5-a)pyrimidine derivatives

Trapidil and some other 5,7-disubstituted s-triazolo(l,5-a)pyrimidine derivatives (TPDs) which were shown to have potent actions against platelet aggregation also inhibited in vitro platelet thromboxane A₂ (TXA₂) biosynthesis in clotting human and rabbit whole blood as well as in arachidonic acid-activated platelet-rich human plasma. The inhibitory potency of TPDs on TXB2 formation paralleled the antiaggregatory effectiveness to a certain extent and decreased in the following order: AR 12456 > AR 12463 ≈ AR 12464 ≈AR 12465 > trapidil. When TPDs were administered orally to rabbits and blood was taken 2 hours later, no changes of serum TXB₂ level were observed. After i.v. injection of TPDs in rabbits, the most active TPDs AR 12456 and AR 12463 led to a short-lasting reduction of serum TXB₂ by 61.4 and 49.4 %, resp.. The TXB₂ levels returned nearly to pre-treatment level after 80 min. The possibility is discussed that TPDs mainly prevent platelet TXA₂ formation by inhibiting phosphodiesterase activity.