非ステロイド性鎮痛抗炎症薬2-{4-(2-Imidazo[1,2-α]pyridyl)phenyl}-propionic Acid(Miroprofen)の血小板凝集およびProstaglandin I<SUB>2</SUB>産生に対する抑制作用

Abstract

Addition of adenosine diphosphate (2 μM) and adrenaline (5 μM) to human plateletrich plasma (PRP) resulted in biphasic aggregation in vitro. The preincubation of 2-{4-(2-imidazo [1, 2-α] pyridyl) phenyl} propionic acid (miroprofen) with PRP showed a dose-dependent inhibition of the second phase but not of the first phase. Rabbit platelet aggregation (PA) with a concomitant malondialdehyde (MDA) formation induced by arachidonic acid (AA, 0.5 mM) was inhibited by miroprofen and acetylsalicylic acid (ASA). The concentration of miroprofen causing a 50% inhibition of PA and MDA formation was 0.154 and 0.121 μg/ml, and about 30 and 50 times as potent as that of ASA respectively. Oral treatment of rabbit with miroprofen and ASA resulted in inhibition of AA-induced PA and generation of prostaglandin I2-like material (PGI2) from vessel walls. The duration of miroprofen-induced inhibition of PA was longer than that of PGI2 generation at doses of 1 and 3 mg/kg. At a dose of 3 mg/kg of miroprofen, inhibition of PA lasted up to 24 h. When ASA was treated with 100 mg/kg inhibition of PA was shorter than that of PGI2 generation, whereas inhibition of PA lasted slightly longer than that of PGI2 generation at a dose of 10 mg/kg. These results suggest that miroprofen inhibits the prostaglandin synthetic pathway of platelets more selectively than that of the vessel wall, and that it may have an antithrombotic activity.