Inhibited Rabbit Platelet Aggregation Research Articles

Studies on anti-atherosclerotic agents. X. Mode of action of eg-626 (7-ethoxycarbonyl-4-hydroxymethyl-6, 8-dimethyl-1 (2h)-phthalazinone) on platelet aggregation.

EG-626 (7-ethoxycarbonyl-4-hydroxymethyl-6, 8-dimethyl-1 (2H)-phthalazinone) is a newly synthesized anti-atherosclerotic and anti-aggregatory agent. The mode of inhibitory action of EG-626 on arachidonic acid (AA)-induced rabbit platelet aggregation was studied in relation to its antagonistic effect on the action of thromboxane (TX) A2, and the following results were obtained.EG-626 in a dose of 3 to 100μg/ml inhibited sodium arachidonate (SAA)-, ADP-, or collagen-induced rabbit platelet aggregation in a concentration dependent manner, 8 and 50μg/ml inhibited rabbit platelet aggregation induced by TXA2 generated by prostaglandin (PG) H2 and platelet microsomes and 10 and 60μg/ml markedly inhibited rabbit platelet aggregation induced by labile aggregation-stimulating substance (LASS). However, a dose of 100μg/ml had no discernible inhibitory effect on the conversion of AA to its metabolites using washed platelet suspension. In addition, EG-626 inhibited the contractile response of aortic strips to TXA2, without affecting TXA2-formation.These results suggest that EG-626 inhibits AA-induced rabbit platelet aggregation primarily through an antagonistic effect on the actions of TXA2 and other active metabolites of AA, without affecting their biosynthesis in platelets.

Anti-platelet aggregating and disaggregating activities of 6,9-methano PGI 2

Anti-platelet aggregating and disaggregating activities of the chemically stable 6,9-methano prostaglandin I 2 (6,9-methano PGI 2) were investigated. 6,9-Methano PGI 2 inhibited ADP-induced platelet aggregation in PRP from humans, rabbits and rats. 6,9-Methano PGI 2 also inhibited rabbit platelet aggregation induced by ADP, collagen, thrombin, arachidonic acid and 11,9-epoxy-methano PGH 2. Antiaggregating activities of 6,9-methano PGI 2 were 0.3 to 2.0 times greater than those of PGE 1. 6,9-Methano PGI 2 facilitated platelet disaggregation in a dose related manner. Antiaggregating and disaggregating activities of 6,9-methano PGI 2 were markedly enhanced by incubation with the phosphodiesterase inhibitor, theophylline.