Frederickson R C, Slater I H, Dusenberry W E, Hewes C R, Jones G T, Moore R A
J Pharmacol Exp Ther. 1977 Oct;203(1):240-51.
We have compared the sleep-producing effects of thalidomide and pentobarbital. In a dose range that did not produce ataxia, thalidomide increased slow wave sleep and rapid eye movement sleep in cats (2-8 mg/kg p.o.) and rats (16 mg/kg p.o.). Pentobarbital had hypnotic activity in the same dose range but produced ataxia also at these doses. Thalidomide reduced spontaneous activity of both mice and rats. This occurred over a dose range of 8 to 1000 mg/kg p.o., but plateaued at a level of activity well above the complete inactivity of anesthesia that occurred with pentobarbital at well above the complete inactivity of anesthesia that occurred with pentobarbital at doses (greater than or equal to 32 mg/kg p.o.) above the hypnotic range. Several simple screens for thalidomide-like activity have been described which, together, could facilitate the search for thalidomide-like hypnotics. Pentobarbital, at doses 3 to 10 times the hypnotic range, prevented audiogenic seizures in physically dependent rats withdrawn from sodium barbital but thalidomide did not substitute for barbiturates even at doses 30 times those that increased sleep. Thalidomide, but not pentobarbital, enhanced the sleep-producing effect of electrical stimulation of basal forebrain in cats. The latter two findings suggest that thalidomide probably has a mechanism of action different from that of pentobarbital and that this may involve the activation of a sleep center in the forebrain.
我们比较了沙利度胺和戊巴比妥的助眠效果。在不会引起共济失调的剂量范围内，沙利度胺可增加猫（口服剂量2 - 8毫克/千克）和大鼠（口服剂量16毫克/千克）的慢波睡眠和快速眼动睡眠。戊巴比妥在相同剂量范围内具有催眠活性，但在这些剂量下也会引起共济失调。沙利度胺可降低小鼠和大鼠的自发活动。这发生在口服剂量8至1000毫克/千克的范围内，但在高于戊巴比妥产生完全麻醉性无活动状态（口服剂量大于或等于32毫克/千克，高于催眠范围）时，沙利度胺的活动水平稳定在远高于完全无活动状态的水平。已经描述了几种针对沙利度胺样活性的简单筛选方法，这些方法共同有助于寻找沙利度胺样催眠药。在从巴比妥钠撤药的身体依赖大鼠中，戊巴比妥在催眠范围的3至10倍剂量下可预防听源性惊厥，但即使沙利度胺的剂量是增加睡眠剂量的30倍，也不能替代巴比妥类药物。沙利度胺而非戊巴比妥可增强猫脑基底前脑电刺激的助眠效果。后两个发现表明，沙利度胺的作用机制可能与戊巴比妥不同，这可能涉及前脑睡眠中枢的激活。
