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氯硝柳胺:一种通过代谢型谷氨酸受体(mGluRs)调节血清素途径的潜在止痒剂。

"Niclosamide: A potential antipruritic agent by modulating serotonin pathway through metabotropic glutamate receptors (mGluRs)".

作者信息

Ebrahim Soltani Zahra, Elahi Mohammad, Askari Rad Maziyar, Farsio Sara, Dehpour Ahmad Reza

机构信息

Experimental Medicine Research Center, Tehran University Medical Science, Tehran, Iran.

Center for Orthopedic Trans-disciplinary Applied Research, Tehran University of Medical Science, Tehran, Iran.

出版信息

Heliyon. 2024 Jun 14;10(12):e33050. doi: 10.1016/j.heliyon.2024.e33050. eCollection 2024 Jun 30.

Abstract

Pruritus is an uncomfortable sensation induced by various pruritogens, including serotonin. Serotonin, acting as an inflammatory mediator, can activate a histamine-independent pathway. Consequently, many anti-pruritus medications, such as antihistamines, are not effective in adequately relieving patient symptoms. Niclosamide, an anthelmintic drug, has recently demonstrated an affinity for Metabotropic glutamate receptors (mGluRs). mGluRs are a group of receptors activated by glutamate, and they are involved in regulating neuronal excitability. In this study, we utilized mouse models of serotonergic itch and administered different doses of Niclosamide to examine the expression of mGluR1, mGluR5, and 5-HT2. The administration of 5 mg/kg Niclosamide successfully suppressed pruritus in the mice. Additionally, the levels of mGluR1, mGluR5, 5-HT2, and TRPV1 were significantly reduced. These findings suggest that Niclosamide holds promise as a potential antipruritic drug.

摘要

瘙痒是由包括血清素在内的各种致痒原引起的一种不适感。血清素作为一种炎症介质,可激活一条不依赖组胺的途径。因此,许多止痒药物,如抗组胺药,在充分缓解患者症状方面并不有效。氯硝柳胺是一种驱虫药,最近已证明其对代谢型谷氨酸受体(mGluRs)具有亲和力。mGluRs是一组由谷氨酸激活的受体,它们参与调节神经元兴奋性。在本研究中,我们利用血清素能性瘙痒的小鼠模型,给予不同剂量的氯硝柳胺,以检测mGluR1、mGluR5和5-HT2的表达。给予5mg/kg氯硝柳胺成功抑制了小鼠的瘙痒。此外,mGluR1、mGluR5、5-HT2和TRPV1的水平显著降低。这些发现表明氯硝柳胺有望成为一种潜在的止痒药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c45/11238049/711d450d1a19/gr1.jpg

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