Volz H-P, Stoll K D
Krankenhaus für Psychiatrie und Psychotherapie Schloss Werneck, Balthasar-Neumann-Platz 1, D-97440 Werneck, Germany.
Pharmacopsychiatry. 2004 Nov;37 Suppl 3:S214-20. doi: 10.1055/s-2004-832680.
So far, sigma-ligands have been investigated for several indications in human studies in functional diarrhea as a model of somatoform disorder (igmesine), depression (igmesine, opipramol), anxiety (opipramol and--in animal models--siramisine), schizophrenia (panamasine, SL 82.0715, rimcazole, DuP 734, BMY 14 802), and somatoform disorders (opipramol). Results for schizophrenia failed to be clear cut and so investigations have apparently stopped for the time being. The Sigma-1-selective igmesine (200 mg) showed good results in a phase-1-model of functional diarrhea and some promising results in depressed patients. However, further development has been stopped due to marketing reasons, which is also true for siramasine, a selective sigma-2-ligand with anxiolytic properties. Opipramol, which, apart from a sigma-1- and 2-receptor liability, also possesses histamine-H(1)-antagonistic properties in connection with lower affinities for D(2) and 5-HT(2A) showed broad efficacy in generalized anxiety disorder and somatoform disorders. The receptor profile of opipramol and the results of studies of the selective sigma site ligands siramisine and igmesine suggest that opipramol acts pharmacologically and clinically via sigma receptors.
迄今为止，在人体研究中，已对西格玛配体在多种适应症中的作用进行了研究，这些适应症包括作为躯体形式障碍模型的功能性腹泻（伊格美新）、抑郁症（伊格美新、奥匹哌醇）、焦虑症（奥匹哌醇以及在动物模型中的西拉米辛）、精神分裂症（帕纳马辛、SL 82.0715、利姆卡唑、DuP 734、BMY 14802）以及躯体形式障碍（奥匹哌醇）。精神分裂症方面的研究结果并不明确，因此相关研究目前显然已暂停。西格玛-1选择性伊格美新（200毫克）在功能性腹泻的1期模型中显示出良好效果，在抑郁症患者中也取得了一些有前景的结果。然而，由于市场原因，其进一步开发已停止，具有抗焦虑特性的选择性西格玛-2配体西拉米辛也是如此。奥匹哌醇除了具有西格玛-1和西格玛-2受体作用外，还具有组胺-H(1)拮抗特性，对D(2)和5-HT(2A)的亲和力较低，在广泛性焦虑症和躯体形式障碍中显示出广泛疗效。奥匹哌醇的受体特征以及对选择性西格玛位点配体西拉米辛和伊格美新的研究结果表明，奥匹哌醇在药理和临床作用上是通过西格玛受体发挥的。
