塩酸ビフェメランの抗血小板作用

Abstract

We investigated the erect of bifemelane hydrochloride on human platelet aggregation and platelet cyclic nucleotide metabolism in order to elucidate its mechanism. Bifemelane inhibited platelet aggregation induced by collagen and ADP with an IC50 value of 6.6×10-5M and 1.2×10-4M, respectively. The inhibitive effects of the agent on platelet aggregation increased in the presence of 10-9M PGI2. Bifemelane significantly increased platelet adenylate cyclase activity in concentrations of 10-5M and 10-4M and inhibited cyclic AMP phosphodiesterase activity with an IC50 value of 6.6×10-4M. Cyclic AMP accumulation in intact platelets in response to bifemelane alone significantly increased only in high concentrations of 10-3M. However, a synergistic effect on cyclic AMP accumulation was found between the bifemelane and PGI2. Although a concentration of 10-4M of bifemelane had no effect on guanylate cyclase activity it did attenuate activity at 10-3M. Bifemelane inhibited cyclic GMP phosphodiesterase activity with an IC50 value similar to cyclic AMP phosphodiesterase (4.5×10-4M). Bifemelane up to a concentration of 10-4M, did not alter cyclic GMP accumulation. However, bifemelane in a concentration 10-4M did decrease activity.We conclude that bifemelane hydrochloride inhibits human platelet aggregation by modulating the cyclic AMP metabolism. Synergism between bifemelane and prostacyclin may also contribute to the enhancement of the antiplatelet action of bifemelane in vivo.