Rovati A L, Vidal y Plana R R, Casula P L, Bizzarri D, Makovec F, Setnikar I
Arzneimittelforschung. 1979;29(8):1116-22.
The pharmacological activities of 3'-(4-[2-(1-p-chlorobenzoyl-5-methoxy-2-methyl-indol-3-yl-acetoxy)-ethyl]-piperazin-1-yl)propyl-4-benzamido-N,N-dipropylglutaramate(+/-)dimaleate (protacine, CR 604), a new indolyl derivative with strong anti-inflammatory, analgesic and antipyretic activities, are described. The dose-dependent activity of protacine on inflammation has been shown both in short-term experiments, like the hind paw edema induced by carrageenin and several other irritants, and long-term tests, like the aminoacetonitrile-induced osteolathyrism, the adjuvant-induced arthritis and the cotton pellet-induced granuloma. The analgesic activity of the drug has been evidenced in the phenylquinone-induced writhing and the Randall-Selitto tests, and the antipyretic effects in the yeast-induced hyperthermia in rats. Other general pharmacological effects have been studied, too. Contrarily to several other anti-inflammatory drugs, including indometacin, showing advers effects at doses which are in the same range of those active on experimental inflammation, protacine shows these effects to a minor degree and at doses which are much larger than those pharmacologically active. The therapeutic index of protacine therefore is superior to that of other anti-inflammatory drugs.
描述了3'-（4-[2-（1-对氯苯甲酰基-5-甲氧基-2-甲基吲哚-3-基乙酰氧基）-乙基]-哌嗪-1-基）丙基-4-苯甲酰胺基-N，N-二丙基谷氨酸盐（+/-）二马来酸盐（protacine，CR 604）的药理活性，它是一种具有强大抗炎、镇痛和解热活性的新型吲哚衍生物。Protacine对炎症的剂量依赖性活性已在短期实验中得到证实，如角叉菜胶和其他几种刺激物诱导的后爪水肿，以及长期试验中，如氨基乙腈诱导的骨软化症、佐剂诱导的关节炎和棉球诱导的肉芽肿。该药物的镇痛活性在苯醌诱导的扭体试验和Randall-Selitto试验中得到证明，其解热作用在酵母诱导的大鼠体温升高中得到体现。还研究了其他一般药理作用。与包括吲哚美辛在内的其他几种抗炎药物相反，这些药物在对实验性炎症有活性的相同剂量范围内显示出不良反应，而protacine在比药理活性剂量大得多的剂量下才显示出较小程度的这些作用。因此，protacine的治疗指数优于其他抗炎药物。
