Yokota K, Yamamoto N, Morimoto Y, Yamashita A, Oda M
New Drug Research Laboratories, Kanebo, Ltd., Osaka, Japan.
J Pharm Pharmacol. 1995 Sep;47(9):768-74. doi: 10.1111/j.2042-7158.1995.tb06739.x.
The effects of KBT-3022 and its metabolite desethyl KBT-3022 on platelet aggregation were determined in rat, guinea-pig, rabbit and human platelets in-vitro and ex-vivo. KBT-3022 and desethyl KBT-3022 inhibited platelet aggregation induced by arachidonic acid and collagen in-vitro more potently than aggregation induced by adenosine diphosphate, platelet-activating factor or thrombin, as well as by acetylsalicylic acid, and their effects were approximately 100 times more potent than those of acetylsalicylic acid. Desethyl KBT-3022, but not KBT-3022 or acetylsalicylic acid, inhibited thrombin-induced aggregation and 5-hydroxytryptamine release from platelets more potently than ticlopidine hydrochloride at higher concentrations. Oral administration of KBT-3022 inhibited both arachidonic acid- and collagen-induced platelet aggregation and reduced platelet retention in a glass-bead column approx. 100 times more potently than acetylsalicylic acid. KBT-3022 showed little or no anti-inflammatory effect on either ultraviolet-induced erythema or arachidonic acid induced ear oedema, and had lower gastro-ulcerogenicity than acetylsalicylic acid. These results suggest that KBT-3022 is a potent inhibitor of platelet activation with weak side-effects.
在大鼠、豚鼠、兔和人血小板中，通过体内和体外实验测定了KBT - 3022及其代谢产物去乙基KBT - 3022对血小板聚集的影响。KBT - 3022和去乙基KBT - 3022在体外抑制花生四烯酸和胶原蛋白诱导的血小板聚集的能力，比抑制二磷酸腺苷、血小板活化因子或凝血酶以及乙酰水杨酸诱导的聚集的能力更强，并且它们的作用效力比乙酰水杨酸大约强100倍。在较高浓度下，去乙基KBT - 3022而非KBT - 3022或乙酰水杨酸，比盐酸噻氯匹定更有效地抑制凝血酶诱导的血小板聚集和5 - 羟色胺释放。口服KBT - 3022抑制花生四烯酸和胶原蛋白诱导的血小板聚集，并且使玻璃珠柱中的血小板滞留减少，其效力比乙酰水杨酸大约强100倍。KBT - 3022对紫外线诱导的红斑或花生四烯酸诱导的耳部水肿几乎没有抗炎作用，并且其致胃溃疡性比乙酰水杨酸低。这些结果表明，KBT - 3022是一种强效的血小板活化抑制剂，副作用较弱。
