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  • Title: Inhibition of thromboxane B2 formation of blood platelets by trapidil and other s-triazolo(1,5-a)pyrimidine derivatives.
    Author: Block HU, Hoffmann-Heinroth I, Taube C, Niebisch M, Mest HJ.
    Journal: Prostaglandins Leukot Med; 1987 Dec; 30(2-3):77-86. PubMed ID: 2827193.
    Abstract:
    Trapidil and some other 5,7-disubstituted s-triazolo(1,5-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 greater than AR 12463 approximately AR 12464 approximately AR 12465 greater than 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.
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