摘要
褪黑素(MLT)与多种病理生理状态有关,包括疼痛。MLT主要激活两种G蛋白偶联受体MT1和MT2.在这篇综述中,我们将介绍止痛剂的研究进展。MLT在临床前和临床研究中的作用,特别强调MT2受体介导的作用,以及最近有关MT2受体镇痛作用的研究。r部分激动剂在慢性和急性/炎性疼痛条件下。MT2受体定位于特定的脑区,包括丘脑的网状核和腹内侧核(部分)。上行伤害感受通路)和中脑导水管周围灰质腹外侧区(下降性抗伤害感受通路的一部分)。MLT对几种动物的镇痛作用慢性、急性、炎症性和神经性疼痛的GMs;重要的是,这些作用是由MT2受体介导的,因为它们被选择性MT2拮抗剂所阻断。在不同的疼痛范式中,UCM924和UCM 765是两种选择性MT2受体部分激动剂,具有比MLT更强的镇痛作用,从而证实MT2受体参与疼痛。值得注意的是,这些化合物不要引起镇静和运动障碍。虽然它们的镇痛作用机制尚未完全阐明,但它们通过刺激MT2受体在抗接种性下行通路上发挥作用。S在vlPAG的谷氨酸能神经元上,而谷氨酸能神经元又激活细胞外,抑制延髓吻端腹内侧区(RVM)细胞。总的来说,有强有力的临床前证据表明MT2受体部分激动剂的药理潜力也具有良好的毒理学特征。这些化合物可能会进一步发展成为新的止痛药。
关键词: 褪黑素,MT2受体,MT2受体部分激动剂,开关细胞,慢性疼痛,急性/炎性疼痛。
Current Medicinal Chemistry
Title:Targeting Melatonin MT2 Receptors: A Novel Pharmacological Avenue for Inflammatory and Neuropathic Pain
Volume: 25 Issue: 32
关键词: 褪黑素,MT2受体,MT2受体部分激动剂,开关细胞,慢性疼痛,急性/炎性疼痛。
摘要: Melatonin (MLT) has been implicated in several pathophysiological states, including pain. MLT mostly activates two G-protein coupled receptors, MT1 and MT2. In this review, we present the analgesic properties of MLT in preclinical and clinical studies, giving particular emphasis to the effects mediated by MT2 receptors and to recent investigations demonstrating the analgesic effects of MT2 receptor partial agonists in chronic and acute/inflammatory pain conditions. MT2 receptors are localized in specific brain areas, including the reticular and the ventromedial nuclei of the thalamus (part of the ascending nociceptive pathway) and the ventrolateral periaqueductal grey matter (vlPAG) (part of the descending antinociceptive pathway). MLT displays analgesic properties in several animal paradigms of chronic, acute, inflammatory and neuropathic pain; importantly, these effects are mediated by MT2 receptors since they are blocked by selective MT2 antagonists. In different pain paradigms, UCM924 and UCM765, two selective MT2 receptor partial agonists, produce analgesic effects with higher potency than MLT, thus confirming the involvement of MT2 receptors in pain. Notably, these compounds do not induce sedation and motor impairments. Although their analgesic mechanism of action is not yet completely elucidated, they act on antinociceptive descending pathways by stimulating MT2 receptors on glutamatergic neurons of the vlPAG, which in turn activate OFF cells and inhibit ON cells of the rostral ventromedial medulla (RVM). Collectively, there is strong preclinical evidence suggesting the pharmacological potential of MT2 receptor partial agonists, which also have a favorable toxicological profile. These compounds may be further developed as novel analgesic drugs.
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Cite this article as:
Targeting Melatonin MT2 Receptors: A Novel Pharmacological Avenue for Inflammatory and Neuropathic Pain, Current Medicinal Chemistry 2018; 25 (32) . https://dx.doi.org/10.2174/0929867324666170209104926
DOI https://dx.doi.org/10.2174/0929867324666170209104926 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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