OPIOID ANALGESICS: PHARMACOLOGICAL & BEHAVIORAL FACTORS

阿片类药物是已知的缓解疼痛的最有效的药物;然而， 它们的临床应用受到许多不希望的作用的限制 作为生产的宽容，身体依赖和倾向， 被虐待 大量的研究致力于开发 阿片类镇痛剂，身体依赖性和滥用倾向低。 在 就这一点而言，部分激动剂和激动剂-拮抗剂已经显示 一些实用的类比;然而，其中一些焦虑的影响， 药物限制了它的使用。 这里提出的实验的目的是 检查所选部分激动剂的行为药理学， 混合激动剂-拮抗剂作为镇痛剂。 这将通过检查 在松鼠猴中进行休克滴定程序的药物数量， 在化合物的形状方面进行比较， 剂量效应曲线，它们被拮抗的难易程度和 它们之间存在交叉耐受性。 化合物选择用于 检查包括部分激动剂丁丙诺啡和picenadol， 推定的κ激动剂布马佐辛、纳布啡和U-50，488， σ激动剂N-烯丙基去甲唑辛的单独异构体。 这些 化合物将被单独检查和在各种阿片样物质存在下检查 拮抗剂被认为在μ、κ或δ上具有不同的活性 受体。 此外，非阿片类镇痛药可乐定将在 考察 最后，用于评估镇痛的刺激类型将是 作为药物效果的决定因素。

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.