Pharmacology and therapeutic potential of sigma(1) receptor ligands.
Pharmacology and therapeutic potential of sigma(1) receptor ligands.
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DOI：
10.2174/157015908787386113
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发表时间：
2008-12
影响因子：
5.3
通讯作者：
Del Pozo E
中科院分区：
文献类型：
--
作者：
Cobos EJ;Entrena JM;Nieto FR;Cendán CM;Del Pozo E
Sigma（σ）受体最初被描述为阿片受体的一种亚型，现在被认为是独特的受体。药理学研究区分了两种类型的σ受体，称为σ1和σ2。在这两种亚型中，σ1受体已在人类和啮齿动物中克隆，其氨基酸序列与其他哺乳动物蛋白质没有同源性。几种精神活性药物对σ1受体表现出高度至中度的亲和力，包括抗精神病药物氟哌啶醇、抗抑郁药物氟伏沙明和舍曲林以及精神兴奋剂可卡因和甲基苯丙胺;此外，抗惊厥药物苯妥英对σ1受体具有变构调节作用。已知某些神经甾体与σ1受体相互作用，并已被认为是其内源性配体。这些受体位于质膜和亚细胞膜中，特别是在内质网中，它们在细胞内Ca 2+信号传导中起调节作用。Sigma 1受体还在一些离子通道和几种神经递质系统的活性中发挥调节作用，主要是在多巴胺能神经传递中。根据其广泛的调节作用，已经提出σ1受体配体可用于几个治疗领域，例如健忘症和认知缺陷、抑郁和焦虑、精神分裂症、镇痛，以及对抗滥用药物（例如可卡因和甲基苯丙胺）的一些作用。在这篇综述中，我们提供了一个概述的σ1受体的现有知识，集中在σ1配体神经药理学和σ1受体在行为动物研究中的作用，这极大地促进了σ1配体的潜在治疗应用。
Sigma (σ) receptors, initially described as a subtype of opioid receptors, are now considered unique receptors. Pharmacological studies have distinguished two types of σ receptors, termed σ1 and σ2. Of these two subtypes, the σ1 receptor has been cloned in humans and rodents, and its amino acid sequence shows no homology with other mammalian proteins. Several psychoactive drugs show high to moderate affinity for σ1 receptors, including the antipsychotic haloperidol, the antidepressant drugs fluvoxamine and sertraline, and the psychostimulants cocaine and methamphetamine; in addition, the anticonvulsant drug phenytoin allosterically modulates σ1 receptors. Certain neurosteroids are known to interact with σ1 receptors, and have been proposed to be their endogenous ligands. These receptors are located in the plasma membrane and in subcellular membranes, particularly in the endoplasmic reticulum, where they play a modulatory role in intracellular Ca2+ signaling. Sigma1 receptors also play a modulatory role in the activity of some ion channels and in several neurotransmitter systems, mainly in glutamatergic neurotransmission. In accordance with their widespread modulatory role, σ1 receptor ligands have been proposed to be useful in several therapeutic fields such as amnesic and cognitive deficits, depression and anxiety, schizophrenia, analgesia, and against some effects of drugs of abuse (such as cocaine and methamphetamine). In this review we provide an overview of the present knowledge of σ1 receptors, focussing on σ1 ligand neuropharmacology and the role of σ1 receptors in behavioral animal studies, which have contributed greatly to the potential therapeutic applications of σ1 ligands.
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影响因子：
5
作者：
Bucolo, C;Marrazzo, A;Drago, F
通讯作者：
Drago, F
影响因子：
5
作者：
Brammer, Matthew K.;Gilmore, Deborah L.;Matsumoto, Rae R.
通讯作者：
Matsumoto, Rae R.
影响因子：
7.3
作者：
Bermack, JE;Debonnel, G
通讯作者：
Debonnel, G
影响因子：
3.4
作者：
Castner, SA;Goldman-Rakic, PS;Williams, GV
通讯作者：
Williams, GV
影响因子：
4.5
作者：
AKIYAMA, K;KANZAKI, A;UJIKE, H
通讯作者：
UJIKE, H