Translational value of non-human primates in opioid research.
Translational value of non-human primates in opioid research.
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DOI：
10.1016/j.expneurol.2021.113602
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发表时间：
2021-04
影响因子：
5.3
通讯作者：
Ko MC
中科院分区：
文献类型：
--
作者：
Ding H;Ko MC
使用动物模型的临床前阿片类药物研究不仅提供了对阿片类药物镇痛及其相关副作用的调节机制的见解，而且还验证了改善阿片类药物使用障碍治疗选择的候选药物。非人灵长类动物（NHP）在阿片类药物研究中作为人类的替代物种已有50多年。啮齿类动物和灵长类动物对阿片类药物相关配体的行为和生理反应存在物种差异，NHP模型的翻译价值得到了证实，NHP研究提供了与人类研究更一致的结果。本文综述了NHP模型在阿片类药物研究中的五个方面的应用，即，镇痛、滥用倾向、呼吸抑制、身体依赖和瘙痒。最近的NHP研究发现，（1）混合μ阿片类药物和痛敏肽/阿片肽受体部分激动剂似乎是安全的、非成瘾性镇痛剂，（2）基于μ阿片类受体和混合阿片类受体亚型的药物仍然是仅有的两类有效缓解阿片类药物诱导的不良反应的药物。鉴于药物科学的最新进展和新靶点的发现，NHP研究提出了确定翻译差距和验证治疗阿片类药物使用障碍的治疗靶点。使用NHP的药理学研究沿着多种结局指标（例如，行为、生理功能和神经影像学）将继续促进改进药物的研究和开发，以遏制阿片类药物的流行。
Preclinical opioid research using animal models not only provides mechanistic insights into the modulation of opioid analgesia and its associated side effects, but also validates drug candidates for improved treatment options for opioid use disorder. Non-human primates (NHPs) have served as a surrogate species for humans in opioid research for more than five decades. The translational value of NHP models is supported by the documented species differences between rodents and primates regarding their behavioral and physiological responses to opioid-related ligands and that NHP studies have provided more concordant results with human studies. This review highlights the utilization of NHP models in five aspects of opioid research, i.e., analgesia, abuse liability, respiratory depression, physical dependence, and pruritus. Recent NHP studies have found that (1) mixed mu opioid and nociceptin/orphanin FQ peptide receptor partial agonists appear to be safe, non-addictive analgesics and (2) mu opioid receptor- and mixed opioid receptor subtype-based medications remain the only two classes of drugs that are effective in alleviating opioid-induced adverse effects. Given the recent advances in pharmaceutical sciences and discoveries of novel targets, NHP studies are posed to identify the translational gap and validate therapeutic targets for the treatment of opioid use disorder. Pharmacological studies using NHPs along with multiple outcome measures (e.g., behavior, physiologic function, and neuroimaging) will continue to facilitate the research and development of improved medications to curb the opioid epidemic.
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影响因子：
4.5
作者：
Ding H;Kiguchi N;Kishioka S;Ma T;Peters CM;Ko MC
通讯作者：
Ko MC
影响因子：
8.2
作者：
BRADY, JV
通讯作者：
BRADY, JV
影响因子：
7.3
作者：
Almatroudi, Abdulrahman;Ostovar, Mehrnoosh;Bailey, Sarah J.
通讯作者：
Bailey, Sarah J.
DOI：
10.1124/jpet.111.189902
发表时间：
2012-05-01
影响因子：
3.5
作者：
Bianchi, Bruce R.;Zhang, Xu-Feng;Chen, Jun
通讯作者：
Chen, Jun
DOI：
10.1124/jpet.103.052381
发表时间：
2003-09-01
影响因子：
3.5
作者：
Butelman, ER;Ball, JW;Kreek, MJ
通讯作者：
Kreek, MJ