Hardt T J, Ritschel W A
Arzneimittelforschung. 1983;33(12):1662-6.
The dose-response relationship upon intraperitoneal administration of coumarin (C) and 7-hydroxycoumarin (7HC) in rats was evaluated using the carrageenan induced edema of the hind paw. In a preliminary study C was indicated to reduce the 4-h edema at doses of 10 to 60 mg/kg i.p. Doses of 2.5 and 5 mg/kg were not effective. In the same study 7HC did not appear to be effective over a dose range of 0.01 to 20 mg/kg. A second study based on a completely randomized design indicated 7HC to be ineffective at doses of 2.5, 5, 10 and 20 mg/kg for edema measurements made at 3, 4, 5 and 6 h after the injury stimulus. C, however, was found to be effective at doses of 5, 10 and 20 mg/kg at 3, 4 and 5 h. C dose of 2.5 mg/kg was ineffective at all times and the 20 mg/kg dose appeared to be ineffective at the 6-h measurement. Resolution of the edema after 5 h did not appear to be enhanced by either C or 7HC administration as the rate of decay appeared to be parallel for controls and the treated animals. The edema model used here would possibly be very useful for further pharmacological investigation of the benzopyrones due to its simplicity, reproducibility and speed.
采用角叉菜胶诱导大鼠后爪水肿模型,评估大鼠腹腔注射香豆素(C)和7-羟基香豆素(7HC)后的剂量-反应关系。在一项初步研究中,腹腔注射剂量为10至60mg/kg的C可减轻4小时后的水肿。2.5和5mg/kg的剂量无效。在同一研究中,剂量范围为0.01至20mg/kg的7HC似乎无效。另一项基于完全随机设计的研究表明,在损伤刺激后3、4、5和6小时测量水肿时,2.5、5、10和20mg/kg剂量的7HC均无效。然而,在3、4和5小时时,5、10和20mg/kg剂量的C被发现有效。2.5mg/kg剂量的C在所有时间均无效,20mg/kg剂量在6小时测量时似乎无效。在5小时后,无论是C还是7HC给药,水肿的消退均未得到增强,因为对照组和治疗组动物的消退速率似乎是平行的。由于其简单性、可重复性和快速性,这里使用的水肿模型可能对苯并吡喃类药物的进一步药理学研究非常有用。