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首页> 外文期刊>Journal of Medicinal Chemistry >Nociceptin Opioid Receptor (NOP) as a Therapeutic Target: Progress in Translation from Preclinical Research to Clinical Utility
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Nociceptin Opioid Receptor (NOP) as a Therapeutic Target: Progress in Translation from Preclinical Research to Clinical Utility

机译:Nociceptin阿片受体(NOP)作为治疗目标:从临床前研究到临床应用的翻译进展

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摘要

In the two decades since the discovery of the nociceptin opioid receptor (NOP) and its ligand, nociceptin/orphaninFQ (N/OFQ), steady progress has been achieved in understanding the pharmacology of this fourth opioid receptor/peptide system, aided by genetic and pharmacologic approaches. This research spawned an explosion of small molecule NOP receptor ligands from discovery programs in major pharmaceutical companies. NOP agonists have been investigated for their efficacy in preclinical models of anxiety, cough, substance abuse, pain (spinal and peripheral), and urinary incontinence, whereas NOP antagonists have been investigated for treatment of pain, depression, and motor symptoms in Parkinson's disease. Translation of preclinical findings into the clinic is guided by PET and receptor occupancy studies, particularly for NOP antagonists. Recent progress in preclinical NOP research suggests that NOP agonists may have clinical utility for pain treatment and substance abuse pharmacotherapy. This review discusses the progress toward validating the NOP-N/OFQ system as a therapeutic target.
机译:自从发现伤害感受素阿片受体(NOP)及其配体伤害感受素/孤儿蛋白FQ(N / OFQ)以来的二十年中,借助遗传学和遗传学方法,在了解第四类阿片受体/肽系统的药理学方面取得了稳步进展。药理学方法。这项研究从主要制药公司的发现计划中引发了小分子NOP受体配体的爆炸式增长。已对NOP激动剂在焦虑,咳嗽,药物滥用,疼痛(脊柱和周围性)和尿失禁的临床前模型中的功效进行了研究,而对NOP拮抗剂已针对帕金森氏病的疼痛,抑郁和运动症状进行了研究。 PET和受体占有率研究(尤其是针对NOP拮抗剂)指导临床前研究结果向临床的转化。临床前NOP研究的最新进展表明,NOP激动剂可能在疼痛治疗和药物滥用药物治疗方面具有临床效用。这篇综述讨论了将NOP-N / OFQ系统验证为治疗目标的进展。

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