Dual antagonism by L-636,499 of serotonin and thromboxane A2 induced aggregation of canine platelets

We evaluated the ability of L-636,499 (3-carboxyl-dibenzo-[b,f] thiepen-5,5-dioxide), a compound structurally similar to cyproheptadine, to antagonize U46619 (a TXA2/PGH2 mimetic) and serotonin (5-hydroxytryptamine; 5HT)-induced aggregation of canine platelets in vitro. L-636,499 antagonized competitively and dose-dependently aggregation induced by both 5HT and U46619, with pA2 values of 5.8 +/- 0.6 and 4.8 +/- 0.2, respectively. L-670,596, a potent TXA2/PGH2 receptor antagonist, and ketanser in, a potent 5HT2 receptor antagonist, yielded pA2 values of 7.0 +/- 0.3 and 9.0 +/- 0.2 vs. their respective agonists. These results show that despite its low potency vs. TXA2- and 5HT2-induced aggregation, L-636,499 antagonizes both physiologic mediators comparably.