Targeting peripheral ϰ-opioid receptors for the non-addictive treatment of pain.
Targeting peripheral ϰ-opioid receptors for the non-addictive treatment of pain.
复制标题
DOI：
10.4155/fdd-2019-0022
复制
发表时间：
2019-10-01
影响因子：
--
通讯作者：
Dix, Thomas A
中科院分区：
文献类型：
--
作者：
Beck, Tyler C;Dix, Thomas A
对用于疼痛的处方μ阿片类激动剂的药物成瘾是一个主要的公共卫生威胁，影响着数百万美国人。κ阿片受体激动剂（KOAs）可能是一种可能的解决方案。在急性和慢性疼痛模型中，KOA已显示出与μ-阿片样物质激动剂不可区分的镇痛活性;然而，常规KOA遭受中枢神经系统介导的精神活性副作用。在这篇综述中，我们讨论了我们的努力，以及其他的努力，在开发外周限制性κ阿片受体激动剂保留或改善啮齿动物疼痛模型的疗效。结果表明，我们的先导化合物JT 09在缓解外周疼痛方面与吗啡一样有效，同时不会产生不希望的中枢神经系统介导的副作用。在这篇综述中，我们讨论了我们以前的结果和未来的发展方向。
Drug addiction to prescription mu-opioid agonists used in the setting of pain is a major public health threat, affecting millions of Americans. Kappa opioid agonists (KOAs) may serve as a possible solution. KOAs have demonstrated indistinguishable analgesic activity relative to mu-opioid agonists in models of acute and chronic pain; however, conventional KOAs suffer from central nervous system-mediated psychoactive side-effects. In this review, we discuss our efforts, as well as other's efforts, in developing peripherally-restricted kappa opioid agonists with retained or improved efficacy in rodent models of pain. Results indicate that our lead compound JT09 acts as efficacious as morphine in alleviating peripheral pain, while failing to produce undesired central nervous system-mediated side-effects. In this review, we discuss our former results and future directions.