Influence of G protein-biased agonists of μ-opioid receptor on addiction-related behaviors.
Influence of G protein-biased agonists of μ-opioid receptor on addiction-related behaviors.
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DOI：
10.1007/s43440-021-00251-1
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Przewlocki R
中科院分区：
文献类型：
--
作者：
Kudla L;Przewlocki R
阿片类镇痛药仍然是治疗中度至重度疼痛的金标准。然而，它们的临床效用受到一系列不良反应的严重限制。其中，它们的高成瘾潜力似乎非常重要，特别是在类阿片流行的情况下。因此，开发更安全、滥用可能性低的阿片类镇痛药成为阿片类药物研究的一个挑战性问题。在过去的几十年中，已经评估了发现新型阿片类药物的不同方法。其中最有前途的是开发G蛋白偏向的阿片激动剂，它只能激活选定的细胞内信号通路。迄今为止，已报道了几种通过μ-阿片受体起作用的偏性激动剂。根据实验数据，这样的配体可以没有至少一些阿片样物质副作用，例如呼吸抑制或便秘。然而，大多数关于偏性μ-阿片受体激动剂成瘾性的数据是不一致的。与阿片类药物滥用有关的全球性问题也需要寻找有效的阿片类药物成瘾药物疗法，这是有偏见的化合物的另一个潜在应用。本文综述了G蛋白偏向的μ阿片受体激动剂的成瘾特性，并分析了这些化合物是否可以减轻阿片成瘾的任何症状。最后，我们提供了一个批判性的观点，最近的数据与偏见的信号及其影响，在体内表现的成瘾。
Opioid analgesics remain a gold standard for the treatment of moderate to severe pain. However, their clinical utility is seriously limited by a range of adverse effects. Among them, their high-addictive potential appears as very important, especially in the context of the opioid epidemic. Therefore, the development of safer opioid analgesics with low abuse potential appears as a challenging problem for opioid research. Among the last few decades, different approaches to the discovery of novel opioid drugs have been assessed. One of the most promising is the development of G protein-biased opioid agonists, which can activate only selected intracellular signaling pathways. To date, discoveries of several biased agonists acting via μ-opioid receptor were reported. According to the experimental data, such ligands may be devoid of at least some of the opioid side effects, such as respiratory depression or constipation. Nevertheless, most data regarding the addictive properties of biased μ-opioid receptor agonists are inconsistent. A global problem connected with opioid abuse also requires the search for effective pharmacotherapy for opioid addiction, which is another potential application of biased compounds. This review discusses the state-of-the-art on addictive properties of G protein-biased μ-opioid receptor agonists as well as we analyze whether these compounds can diminish any symptoms of opioid addiction. Finally, we provide a critical view on recent data connected with biased signaling and its implications to in vivo manifestations of addiction.
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