具有多种临床前治疗活性的系统活性非肽NOP受体(阿片受体样1,ORL-1)激动剂Ro 64-6198的药理学研究

James R. Shoblock
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引用次数: 46

摘要

NOP受体(以前称为阿片受体样1、ORL-1、LC132、OP4或NOP1)是一种G蛋白偶联受体,与经典的阿片受体MOP、DOP和KOP(分别为mu、delta和kappa)具有高度同源性,于1994年由几个研究小组首次克隆。NOP受体一直是孤儿受体,直到1995年,内源性神经肽激动剂,被称为nociceptin或孤儿蛋白FQ (N/OFQ)被分离出来。五年后,霍夫曼-罗氏公司的一个研究小组报道了选择性非多肽NOP激动剂Ro 64-6198,这成为发表最多的非多肽NOP激动剂,也是确定NOP受体作为治疗靶点潜力的有价值的药理学工具。Ro 64-6198具有全身性活性,可实现高脑穿透。它对NOP受体具有亚纳摩尔亲和力,对NOP受体的选择性至少是经典阿片受体的100倍。Ro 64-6198的范围从部分到完全激动剂,取决于测定。临床前数据表明,ro64 -6198可能具有广泛的临床应用,如治疗压力和焦虑、成瘾、神经性疼痛、咳嗽和厌食症。本文综述了ro64 -6198的药理作用和临床前研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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The Pharmacology of Ro 64-6198, a Systemically Active, Nonpeptide NOP Receptor (Opiate Receptor-Like 1, ORL-1) Agonist with Diverse Preclinical Therapeutic Activity

The NOP receptor (formerly referred to as opiate receptor-like 1, ORL-1, LC132, OP4, or NOP1) is a G protein–coupled receptor that shares high homology to the classic opioid MOP, DOP, and KOP (mu, delta, and kappa, respectively) receptors and was first cloned in 1994 by several groups. The NOP receptor remained an orphan receptor until 1995, when the endogenous neuropeptide agonist, known as nociceptin or orphanin FQ (N/OFQ) was isolated. Five years later, a group at Hoffmann-La Roche reported on the selective, nonpeptide NOP agonist Ro 64-6198, which became the most extensively published nonpeptide NOP agonist and a valuable pharmacological tool in determining the potential of the NOP receptor as a therapeutic target. Ro 64-6198 is systemically active and achieves high brain penetration. It has subnanomolar affinity for the NOP receptor and is at least 100 times more selective for the NOP receptor over the classic opioid receptors. Ro 64-6198 ranges from partial to full agonist, depending on the assay. Preclinical data indicate that Ro 64-6198 may have broad clinical uses, such as in treating stress and anxiety, addiction, neuropathic pain, cough, and anorexia. This review summarizes the pharmacology and preclinical data of Ro 64-6198.

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