Takebayashi M, Hayashi T, Su T-P
Cellular Pathobiology Unit, Cellular Neurobiology Research Branch, National Institute on Drug Abuse, NIH/DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
Pharmacopsychiatry. 2004 Nov;37 Suppl 3:S208-13. doi: 10.1055/s-2004-832679.
Sigma receptors were first described as one of the opiate receptor subtypes. Now it is well established that sigma receptors, existing as subtypes sigma-1 and sigma-2, are unique non-opioid receptors which are implicated in higher-ordered brain functions. Sigma-1 receptors have high to moderate affinities for (+)benzomorphans and also many psychotrophic drugs and neurosteroids. Sigma-1 receptor agonists and certain neurosteroids such as dehydroepiandrosterone sulfate (DHEA-S) have antidepressant-like effects in animal behavioral models of depression. The antidepressant-like effect induced by sigma-1 receptor agonists may involve intracellular Ca (2+) mobilization such that sigma-1 receptor agonists modulate Ca (2+) release from endoplasmic reticulum (ER) in a cytoskeletal protein-dependent manner. In addition, growth factor-induced neurite outgrowth is mediated through sigma-1 receptors, suggesting a role of antidepressants in neuroplasticity. Igmesine (JO1783), OPC-14 523 and SA4503, have recently been developed as sigma-1 agonists and are found to have antidepressant-like activity perhaps with fewer side effects. This article reviews the new potential use of sigma-1 receptor ligands in the treatment of mood disorder.
西格玛受体最初被描述为阿片受体亚型之一。现在已经明确，西格玛受体以西格玛-1和西格玛-2亚型的形式存在，是独特的非阿片类受体，与高级脑功能有关。西格玛-1受体对（+）苯吗喃以及许多精神营养药物和神经甾体具有高到中等的亲和力。西格玛-1受体激动剂和某些神经甾体，如硫酸脱氢表雄酮（DHEA-S），在动物抑郁行为模型中具有抗抑郁样作用。西格玛-1受体激动剂诱导的抗抑郁样作用可能涉及细胞内Ca（2+）动员，使得西格玛-1受体激动剂以细胞骨架蛋白依赖性方式调节内质网（ER）的Ca（2+）释放。此外，生长因子诱导的神经突生长是通过西格玛-1受体介导的，这表明抗抑郁药在神经可塑性中起作用。伊格美辛（JO1783）、OPC-14523和SA4503最近被开发为西格玛-1激动剂，并被发现具有抗抑郁样活性，可能副作用较少。本文综述了西格玛-1受体配体在治疗情绪障碍方面的新潜在用途。
