OPIOID ANALGESICS: PHARMACOLOGICAL & BEHAVIORAL FACTORS

阿片类镇痛药：药理学

• 批准号: 3207557
• 负责人: LINDA A DYKSTRA
• 金额: $ 9.88万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-01-01 至 1988-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3207557
• 关键词: analgesics; clonidine; drug addiction antagonist; drug tolerance; electrostimulus; heat stimulus; morphine; naloxone; narcotics; operant conditionings; opiate alkaloid; pain threshold; psychobiology; psychopharmacology; sensory discrimination; stimulus /response

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.

阿片类药物是已知的缓解疼痛最有效的药物；然而， 它们的临床实用性受到许多不良影响的限制，例如 作为耐受性、身体依赖性和倾向的产生 被虐待。 大量的研究致力于开发 阿片类镇痛药具有较低的身体依赖性和滥用倾向。 在 在这方面，部分激动剂和激动剂-拮抗剂已经表明 具有一定的镇痛药效用；然而，其中一些的令人不安的影响 药物限制了它们的使用。 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和 混合激动剂-拮抗剂作为镇痛药。 这将通过检查来完成 松鼠猴休克滴定程序下的药物数量 对化合物之间的形状进行比较 剂量效应曲线、拮抗的难易程度以及 它们之间出现交叉耐受。 选定的化合物 检查包括部分激动剂丁丙诺啡和picenadol， 推定的 kappa 激动剂包括布马佐辛、纳布啡和 U-50、488 以及 sigma 激动剂 n-烯丙基去甲佐辛的单独异构体。 这些 化合物将单独进行检查，并在各种阿片类药物存在的情况下进行检查 拮抗剂被认为在 mu、kappa 或 delta 处具有不同的活性 受体。 此外，非阿片类镇痛药可乐定将 检查了。 最后，用于评估镇痛的刺激类型将是 作为药物作用的决定因素进行检查。