Maruyama Y, Kadobe Y, Imamura H
Nihon Yakurigaku Zasshi. 1976 May;72(4):403-16. doi: 10.1254/fpj.72.403.
This anti-inflammatory agent proved to have a therapeutic margin wider than that of indomethacin. Y-8004 exhibited little effect on the central nervous system, somatic and autonomic nervous system. On the cardiovascular system in dogs, Y-8004 induced a slight transient fall in blood pressure followed by a pressor response, increase in heart rate and coronary vasodilation at a dose of 30 mg/kg given intravenously, but no remarkable change was seen on the electrocardiogram. Y-8004 showed no effect on isolated smooth muscles such as vas deferens, ileum and atria, but inhibited gastrointestinal propulsion at a dose of 100 mg/kg given orally in mice and spontaneous contractions of the pregnant uterus of rats at a concentration of more than 10(-6)M. This agent also decreased urine volume and electrolytes in rats. This property was considered to be common to other acidic nonsteroidal anti-inflammatory agents. On the other hand, in guinea pigs, Y-8004 inhibited the bradykinin-induced bronchoconstriction and the collagen-induced platelet aggregation to a greater extent than did indomethacin. These findings suggest that Y-8004 is an active compound with properties similar to acidic non-steroidal anti-inflammatory agents such as indomethacin.
这种抗炎药的治疗窗比吲哚美辛更宽。Y - 8004对中枢神经系统、躯体和自主神经系统几乎没有影响。在犬的心血管系统上，静脉注射30mg/kg剂量的Y - 8004会引起血压轻微短暂下降，随后出现升压反应、心率增加和冠状血管舒张，但心电图未见明显变化。Y - 8004对输精管、回肠和心房等离体平滑肌无作用，但在小鼠口服100mg/kg剂量时可抑制胃肠推进，在大鼠妊娠子宫浓度高于10(-6)M时可抑制其自发收缩。该药物还可减少大鼠尿量和电解质。这种特性被认为是其他酸性非甾体抗炎药所共有的。另一方面，在豚鼠中，Y - 8004比吲哚美辛更能抑制缓激肽诱导的支气管收缩和胶原诱导的血小板聚集。这些发现表明Y - 8004是一种活性化合物，其性质与吲哚美辛等酸性非甾体抗炎药相似。
