Kakushi H, Shike T, Hayasaki Y, Arita H, Uchida K
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Nihon Yakurigaku Zasshi. 1991 Aug;98(2):113-20. doi: 10.1254/fpj.98.2_113.
The effect of (+)-S-145, (1R, 2S, 3S, 4S)-(5Z)-7-(3-phenylsulfonylaminobicyclo [2.2.1] hept-2-yl) heptenoic acid on human and guinea pig platelet aggregation was examined. (+)-S-145 sodium salt inhibited human platelet aggregation induced by arachidonic acid (AA), 9,11-methanoepoxy-PGH2 (U 46619), collagen, ADP or epinephrine with the IC50 being 0.047-0.146 microM in an in vitro system. When (+)-S-145 calcium salt dihydrate was administered orally to guinea pigs, it inhibited AA-, U-46619- or collagen-induced platelet aggregation dose-dependently with the minimum effective dose being 0.03 mg/kg, and the effective duration being maximally 3 hr. The inhibiting potency and effective duration of (+)-S-145 calcium salt dihydrate after multiple administrations, once a day (0.5 mg/kg) for 7 days, were almost the same as those after a single administration. Although (+)-S-145 sodium salt showed a partial agonist effect (shape change) on platelets in vitro, the effect diminished after pretreatment of the platelets with a lower dose of this compound. These data suggest that (+)-S-145 calcium salt dihydrate is an orally effective potent platelet aggregation inhibitor.
研究了(+)-S-145，即(1R, 2S, 3S, 4S)-(5Z)-7-(3-苯基磺酰氨基双环[2.2.1]庚-2-基)庚烯酸对人和豚鼠血小板聚集的影响。在体外系统中，(+)-S-145钠盐可抑制花生四烯酸(AA)、9,11-亚甲基环氧-PGH2(U 46619)、胶原、ADP或肾上腺素诱导的人血小板聚集，IC50为0.047 - 0.146微摩尔。当给豚鼠口服二水合(+)-S-145钙盐时，它能剂量依赖性地抑制AA、U-46619或胶原诱导的血小板聚集，最小有效剂量为0.03毫克/千克，有效持续时间最长为3小时。多次给药（每天一次，0.5毫克/千克，共7天）后，二水合(+)-S-145钙盐的抑制效力和有效持续时间与单次给药后几乎相同。虽然(+)-S-145钠盐在体外对血小板表现出部分激动剂作用（形态改变），但用较低剂量的该化合物预处理血小板后，这种作用会减弱。这些数据表明，二水合(+)-S-145钙盐是一种口服有效的强效血小板聚集抑制剂。
