Sigma-1 Receptor Agonists and Their Clinical Implications in Neuropsychiatric Disorders
Sigma-1 Receptor Agonists and Their Clinical Implications in Neuropsychiatric Disorders
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DOI：
10.1007/978-3-319-50174-1_11
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发表时间：
2017-01-01
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影响因子：
--
通讯作者：
Hashimoto, Kenji
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文献类型：
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作者：
Albayrak, Yakup;Hashimoto, Kenji
越来越多的证据表明，σ-1受体在神经精神疾病的病理生理学中起作用，以及在一些选择性5-羟色胺再摄取抑制剂（SSRIs）的机制中起作用。在SSRI中，对σ-1受体的亲和力顺序如下：氟伏沙明>舍曲林>氟西汀>依他普仑>西酞普兰>帕罗西汀。一些SSRIs（例如，氟伏沙明、氟西汀和艾司西酞普兰）和其他药物（多奈哌齐、艾芬地尔、脱氢表雄酮（DHEA））增强神经生长因子（NGF）诱导的PC 12细胞中的神经突生长，并且这些作用可以被选择性σ-1受体拮抗剂NE-100拮抗。此外，氟伏沙明，多奈哌齐，DHEA，但不是帕罗西汀或舍曲林，改善苯环己哌啶诱导的小鼠认知缺陷，这些作用可以被NE-100拮抗。几项临床研究表明，sigma-1受体激动剂如氟伏沙明和艾芬地尔对神经精神疾病患者可能具有有益作用。在本章中，作者将讨论sigma-1受体在某些SSRIs、多奈哌齐、神经类固醇和艾芬地尔的机制作用中的作用，以及sigma-1受体激动剂的临床意义。
Accumulating evidence suggests that sigma-1 receptors play a role in the pathophysiology of neuropsychiatric diseases, as well as in the mechanisms of some selective serotonin reuptake inhibitors (SSRIs). Among the SSRIs, the order of affinity for sigma-1 receptors is as follows: fluvoxamine > sertraline > fluoxetine > escitalopram > citalopram >> paroxetine. Some SSRIs (e.g., fluvoxamine, fluoxetine and escitalopram) and other drugs (donepezil, ifenprodil, dehydroepiandeterone (DHEA)) potentiate nerve-growth factor (NGF)-induced neurite outgrowth in PC12 cells, and these effects could be antagonized by the selective sigma-1 receptor antagonist NE-100. Furthermore, fluvoxamine, donepezil, and DHEA, but not paroxetine or sertraline, improved phencyclidine-induced cognitive deficits in mice, and these effects could be antagonized by NE-100. Several clinical studies showed that sigma-1 receptor agonists such as fluvoxamine and ifenprodil could have beneficial effects in patients with neuropsychiatric disorders. In this chapter, the authors will discuss the role of sigma-1 receptors in the mechanistic action of some SSRIs, donepezil, neurosteroids, and ifenprodil, and the clinical implications for sigma-1 receptor agonists.