OPIOID ANALGESICS: PHARMACOLOGICAL & BEHAVIORAL FACTORS

阿片类药物是已知的最有效的止痛药物；然而， 它们的临床应用受到许多不良影响的限制，如 作为宽容的产物，身体上的依赖和一种被 被虐待。已经投入了大量的研究来开发 阿片类镇痛剂，身体依赖性和滥用倾向低。在……里面 在这方面，部分激动剂和激动剂-拮抗剂已经显示出 一些有用的类比；然而，其中一些焦躁不安的效果 毒品限制了他们的使用。这里提出的实验的目的是 检查选定的部分激动剂的行为药理学和 混合激动剂-拮抗剂作为镇痛剂。这将通过检查一个 松鼠猴休克滴定程序中的药物数量和 在化合物的形状方面进行比较 剂量-效应曲线，它们被拮抗的容易程度和 它们之间发生了交叉耐受。选定的化合物 检查包括部分激动剂丁丙诺啡和吡那多， 推定的kappa激动剂Bremazocine，Nalbuphine和U-50,488和 分离Sigma激动剂N-烯丙基去甲氧甲佐辛的异构体。这些 将单独检查化合物以及在存在各种阿片类药物的情况下进行检查 被认为在Mu、Kappa或Delta具有不同活动的对手 感受器。此外，非阿片类止痛药可乐定将 检查过了。最后，用于评估止痛的刺激类型为 作为药物效果的决定因素而被检验。

Opioids are the most effective drugs known for the relief of pain; however, their clinical utility is limited by a number of undesirable effects such as the production of tolerance, physical dependence and a tendency to be abused. A considerable amount of research has been devoted to developing opioid analgesics with low physical dependence and abuse liabilities. In this regard, the partial agonists and the agonist-antagonists have shown some utility as analegics; however, the dysphoric effects of some of these drugs has limited their use. The aim of the experiments proposed here is to examine the behavioral pharmacology of selected partial agonists and mixed agonist-antagonists as analgesics. This will be done by examining a number of drugs under a shock titration procedure in squirrel monkeys and making comparisons between compounds in terms of the shape of their dose-effect curves, the ease with which they are antagonized and the occurrence of cross tolerance among them. Compounds selected for examination include the partial agonists buprenorphine and picenadol, the putative kappa agonists bremazocine, nalbuphine and U-50, 488 and the separate isomers of the sigma agonist n-allyl normetazocine. These compounds will be examined alone and in the presence of various opioid antagonists thought be have varying activity at mu, kappa or delta receptors. In addition, the nonopioid analgesic clonidine will be examined. Finally, the type of stimulus used to assess analgesia will be examined as a determinant of drug effect.