OPIOID ANALGESICS: PHARMACOLOGICAL & BEHAVIORAL FACTORS

药物化学的研究努力产生了阿片类药物和 非阿片类止痛药，可通过以下方式有效缓解疼痛 降低了依赖的可能性。我们的目标是研究 重点介绍了其中一些化合物的镇痛作用 关于被认为对u或kappa阿片类药物有活性的激动剂 受体类型。止痛活性将被评估为2 程序，松鼠猴休克滴定程序和一个 新开发的大鼠热辨别程序。在……里面 此外，还将进行研究，其中 操纵伤害性刺激(电击或热)是为了 确定1)亩或卡帕的影响程度 激动剂取决于刺激强度和2)是否有止痛剂 低效化合物的效果可能会显现出来。 刺激强度。为了进行比较，我们还将研究 几种u和kappa类阿片激动剂对时程的影响 受控制的行为。这些调查将在#年进行。 使松鼠、猴子、大鼠和鸽子的药物有差异 物种之间的影响是可以检验的。此外， Mu和Kappa类阿片激动剂的辨别刺激特性 将在老鼠和鸽子身上进行研究。在所有这些研究中， 重点将放在以下几个方面： 阿片类激动剂的行为效应及其中介作用 通过不同的阿片受体类型发挥作用。为了画出 这种关系，阿片类激动剂将在#年单独检查 与阿片类拮抗剂联合使用并在动物中使其耐受 Mu或Kappa激动剂。然后，我们将对 1)不同的行为特征和效力关系的基础 在阿片激动剂中2)阿片拮抗剂在 减弱这些激动剂的作用和3)发生 他们之间的相互容忍。

Research efforts in medicinal chemistry have produced opioid and nonopioid analgesics which may provide effective pain relief with reduced dependence potential. It is our objective to examine the analgesic effects of a number of these compounds with emphasis on agonists presumed to have activity at mu or kappa opioid receptor types. Analgesic activity will be assessed with 2 procedures, the squirrel monkey shock titration procedure and a newly developed thermal discrimination procedure in rats. In addition, studies will be carried out in which the intensity of the nociceptive stimulus (shock or heat) is manipulated in order to determine 1) the extent to which the effects of mu or kappa agonists depend on stimulus intensity and 2) whether analgesic effects might be revealed for less efficacious compounds at lower stimulus intensities. For comparison, we will also examine the effects of several mu and kappa opioid agonists on schedule- controlled behavior. These investigations will be carried out in squirrel monkeys, rats and pigeons so that differences in drug effects between species can be examined. In addition, the discriminative stimulus properties of mu and kappa opioid agonists will be investigated in rats and pigeons. In all of these studies, emphasis will be placed on the relationship between the behavioral effects of opioid agonists and the mediation of their effects through different opioid receptor types. In order to draw such relationships, opioid agonists will be examined alone, in combination with opioid antagonists and in animals made tolerant to mu or kappa agonists. Comparisons will then be made on the basis of 1) differing behavioral profiles and potency relationships among the opioid agonists 2) the potency of opioid antagonists in attenuating the effects of these agonists and 3) the occurrence of cross tolerance among them.