Effects of NOP-Related Ligands in Nonhuman Primates.
Effects of NOP-Related Ligands in Nonhuman Primates.
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DOI：
10.1007/164_2019_211
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发表时间：
2019
影响因子：
--
通讯作者：
Ko MC
中科院分区：
文献类型：
--
作者：
Kiguchi N;Ko MC
伤害感受素/Nociceptin FQ肽（NOP）受体相关配体已经在临床前研究中被证明用于几种治疗应用。本文重点介绍了（1）如何使用非人灵长类动物（NHP）来促进正电子发射断层扫描示踪剂在人类中的开发和应用;（2）内源性NOP配体的作用，FQ中的伤害感受素/阿片肽，及其与μ阿片肽（MOP）受体激动剂的相互作用;和（3）NHP中NOP相关激动剂作为镇痛剂和治疗物质使用障碍的有前途的功能概况。NHP模型提供了阿片和非阿片受体功能和药物作用的最适合遗传学的评估。基于具有混合NOP/MOP受体激动剂活性的配体的临床前和临床数据，包括其激活NOP与MOP受体的内在功效和NHP中不同的研究终点在内的几个因素可能导致不同的药理学特征。来自NHP研究的充分证据表明，双功能NOP/MOP受体激动剂为开发安全、有效且副作用较少的药物治疗疼痛和药物成瘾开辟了一条令人兴奋的途径。特别是，双功能NOP/MOP部分激动剂具有很大的潜力，可作为（1）有效的脊髓镇痛剂，无瘙痒副作用;（2）安全、非成瘾性镇痛剂，无阿片类药物副作用，如呼吸抑制;和（3）有效的药物用于物质使用障碍。
The nociceptin/orphanin FQ peptide (NOP) receptor-related ligands have been demonstrated in preclinical studies for several therapeutic applications. This article highlights (1) how nonhuman primates (NHP) were used to facilitate the development and application of positron emission tomography tracers in humans; (2) effects of an endogenous NOP ligand, nociceptin/orphanin FQ, and its interaction with mu opioid peptide (MOP) receptor agonists; and (3) promising functional profiles of NOP-related agonists in NHP as analgesics and treatment for substance use disorders. NHP models offer the most phylogenetically appropriate evaluation of opioid and non-opioid receptor functions and drug effects. Based on preclinical and clinical data of ligands with mixed NOP/MOP receptor agonist activity, several factors including their intrinsic efficacies for activating NOP versus MOP receptors and different study endpoints in NHP could contribute to different pharmacological profiles. Ample evidence from NHP studies indicates that bifunctional NOP/MOP receptor agonists have opened an exciting avenue for developing safe, effective medications with fewer side effects for treating pain and drug addiction. In particular, bifunctional NOP/MOP partial agonists hold a great potential as (1) effective spinal analgesics without itch side effects; (2) safe, nonaddictive analgesics without opioid side effects such as respiratory depression; and (3) effective medications for substance use disorders.