activity. Several of these analogues show analgesic potency comparable to morphine in the mouse writhing and tail-flick tests. A number of compounds exhibit high affinity for [3H]naloxone binding sites in rat brain membranes. Among the most potent derivatives are compounds 15 and 48. Although opiate-like, attempts to modify this activity with various substituents have failed to produce antagonistic properties
已经合成了一系列的4,4-二取代的
哌啶并评估了其止痛活性。这些类似物中的几种在小鼠扭动和甩尾试验中显示出与
吗啡相当的镇痛效果。许多化合物对大鼠脑膜中的[3H]
纳洛酮结合位点显示出高亲和力。在最有效的衍
生物中是化合物15和48。尽管是鸦片样的,但尝试用各种取代基修饰该活性未能产生拮抗作用。这些类似物中的一些在豚鼠5-羟
色胺毒性试验中和在小鼠中由DL-5-羟色
氨酸诱导的头抽搐模型中也显示出明显的持久性5-羟
色胺拮抗作用。