Skuza G, Wedzony K
Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland.
Pharmacopsychiatry. 2004 Nov;37 Suppl 3:S183-8. doi: 10.1055/s-2004-832676.
Sigma (sigma) receptors, first defined as a subclass of opioid receptors, later confounded with the high affinity phencyclidine (PCP) binding sites, now are regarded as unique binding sites, distinct from opiate and PCP receptors, and related to higher brain function. The investigation of functional significance of sigma receptors in the brain has been hampered for many years by relative lack of specific tool drugs and by the unavailability of their coherent classification into postulated agonists and antagonists. However, a potential involvement of sigma receptors in psychotic disorders was first suggested soon after their discovery. The sigma receptors are classified into two subtypes, sigma (1) and sigma (2) receptors, of which the first was recently cloned from rodent and human tissues while the second has not yet been fully characterized. Although the precise mechanism of the functional response of these receptors is still uncertain, it is accepted that sigma receptors can modulate a number of central neurotransmitter systems, including noradrenergic, glutamatergic and dopaminergic ones. The sigma receptors have been postulated to be involved in numerous pharmacological and physiological functions, including motor disorders, psychotic disorders, neuroprotective mechanisms. In the last years, a number of compounds with a high affinity and selectivity for sigma binding sites have been discovered and investigated for their therapeutic potential. In this review, we try to summarize the behavioral effects of sigma receptor ligands that have been described, and their activity in animal models related to some brain disorders, especially schizophrenia and affective disorders.
西格玛（sigma）受体最初被定义为阿片受体的一个亚类，后来与高亲和力苯环己哌啶（PCP）结合位点混淆，现在被视为独特的结合位点，与阿片类和PCP受体不同，且与高级脑功能相关。多年来，由于相对缺乏特异性工具药物以及无法将其连贯地分类为假定的激动剂和拮抗剂，对大脑中西格玛受体功能意义的研究受到了阻碍。然而，西格玛受体在精神病性障碍中的潜在作用在其发现后不久就首次被提出。西格玛受体分为两种亚型，西格玛（1）和西格玛（2）受体，其中第一种最近已从啮齿动物和人类组织中克隆出来，而第二种尚未完全表征。尽管这些受体功能反应的确切机制仍不确定，但人们普遍认为西格玛受体可以调节多种中枢神经递质系统，包括去甲肾上腺素能、谷氨酸能和多巴胺能系统。西格玛受体被假定参与多种药理和生理功能，包括运动障碍、精神病性障碍、神经保护机制。在过去几年中，已经发现了许多对西格玛结合位点具有高亲和力和选择性的化合物，并对其治疗潜力进行了研究。在这篇综述中，我们试图总结已描述的西格玛受体配体的行为效应，以及它们在与某些脑部疾病，特别是精神分裂症和情感障碍相关的动物模型中的活性。
