Targeting Itch with Ligands Selective for κ Opioid Receptors
Targeting Itch with Ligands Selective for κ Opioid Receptors
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DOI：
10.1007/978-3-662-44605-8_16
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发表时间：
2015-01-01
期刊：
影响因子：
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通讯作者：
Inan, Saadet
中科院分区：
文献类型：
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作者：
Cowan, Alan;Kehner, George B.;Inan, Saadet
几种化学性质不同的致痒原，包括蛙皮素、化合物48/80、去甲二氢愈创木脂酸和5'-GNTI，能使啮齿动物以稳定、一致的方式过度搔抓，从而为研究瘙痒提供了便利的动物模型，可借此评估潜在的止痒药、建立构效关系以及分析自发重复行为本身的性质。在这些看似简单的模型中减少搔抓次数是κ阿片受体激动剂（如纳布啡、阿西马朵林和CR845）朝着作为止痒药进行临床测试进展的必要第一步。纳呋拉啡是κ激动剂的一个主要例子，它跨越了搔抓小鼠模型与10年内商业化之间的发展鸿沟。接受血液透析且患有与尿毒症瘙痒相关的瘙痒症的患者，以及可能患有特应性皮炎的患者是受益者。
Several chemically diverse pruritogens, including bombesin, compound 48/80, norbinaltorphimine, and 5'-GNTI, cause rodents to scratch excessively in a stable, uniform manner and consequently provide convenient animal models of itch against which potential antipruritics may be evaluated, structure-activity relationships established, and the nature of spontaneous, repetitive behavior itself analyzed. Decreasing the number of scratching bouts in these apparently simple models has been the requisite first step in the progress of kappa opioid agonists such as nalbuphine, asimadoline, and CR845 toward clinical testing as antipruritics. Nalfurafine is the prime example of a kappa agonist spanning the developmental divide between scratching mice models and commercialization within 10 years. Patients undergoing hemodialysis and suffering from the itching associated with uremic pruritus, and potentially those inflicted with atopic dermatitis, are the beneficiaries.