SYNERGISTIC ANTIPLATELET EFFECT OF RIDOGREL, A COMBINED THROMBOXANE RECEPTOR ANTAGONIST AND THROMBOXANE SYNTHASE INHIBITOR, AND UDCG-212, ACAMP-PHOSPHODIESTERASE INHIBITOR

Ridogrel, a combined thromboxane receptor antagonist and thromboxane s ynthase inhibitor (1), inhibits platelet aggregation. Following stimul ation with arachidonic acid, cAMP-levels are increased in human platel ets preincubated with ridogrel, this is due to the known reorientation of the metabolism of the formed endoperoxides towards adenylate cycla se stimulating prostaglandins. Pretreatment of resting platelets with UDCG-212, a cAMP-phosphodiesterase inhibitor (2), also inhibits platel et aggregation induced by arachidonic acid, concomitant with an increa se in cAMP levels, due to an inhibition of its breakdown. Under basal conditions, cAMP also is increased. By combining the two drugs, a more than additive action was observed on platelet aggregation and on both resting and stimulated platelet cAMP content. The appropriate combina tion may result in a more effective antiplatelet strategy.