Nabeshima T, Okuyama S
Department of Neuropsychopharmacology, Nagoya University School of Medicine, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 1994 Apr;14(2):51-76.
N-allylnormetazocine (SKF-10047) and related benzomorphans induce psychotomimetic effects in animals and humans, and bind a unique, non-opioid receptor, denoted the sigma site. Sigma receptors have been found in the cortical and limbic structures in human postmortem brain: their anatomical distribution is different from phencyclidine (PCP) sites. Sigma receptors regulate not only dopamine, excitatory amino acid and PCP receptors, but also interact neuropeptides. Endogenous sigma ligands are not yet determined. Isolation and cloning of the receptor genes have not yet been successful. Selective loss of cerebral cortical sigma, but not PCP binding sites, has been observed in schizophrenia. A more compelling role for sigma sites in schizophrenia is indicated by the high affinity of some neuroleptic drugs, including haloperidol, for sigma sites. Rimcazole, a weak but selective sigma ligand, has very good clinical efficacy as a neuroleptic agent and has few side effects. Thus, sigma ligands may be useful in the treatment of schizophrenia. The present review describes properties of sigma receptors and its roles in relation to sigma ligands in the regulation of the central nervous system on the basis of the results of more recent studies.
N-烯丙基去甲左啡诺（SKF-10047）及相关苯并吗啡烷在动物和人类中可诱发拟精神病效应，并与一种独特的非阿片受体结合，该受体被称为西格玛位点。在人类死后大脑的皮质和边缘结构中发现了西格玛受体：它们的解剖分布与苯环己哌啶（PCP）位点不同。西格玛受体不仅调节多巴胺、兴奋性氨基酸和PCP受体，还与神经肽相互作用。内源性西格玛配体尚未确定。受体基因的分离和克隆尚未成功。在精神分裂症患者中已观察到大脑皮质西格玛位点选择性丧失，但PCP结合位点未丧失。一些抗精神病药物，包括氟哌啶醇，对西格玛位点具有高亲和力，这表明西格玛位点在精神分裂症中具有更重要的作用。利咪唑是一种较弱但具有选择性的西格玛配体，作为一种抗精神病药物具有非常好的临床疗效且副作用较少。因此，西格玛配体可能对精神分裂症的治疗有用。本综述基于最近的研究结果，描述西格玛受体的特性及其在调节中枢神经系统中与西格玛配体相关的作用。
