Can the Sigma-1 Receptor Agonist Fluvoxamine Prevent Schizophrenia?
Can the Sigma-1 Receptor Agonist Fluvoxamine Prevent Schizophrenia?
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DOI：
10.2174/187152709789824633
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发表时间：
2009-12-01
影响因子：
3
通讯作者：
Hashimoto, Kenji
中科院分区：
文献类型：
--
作者：
Hashimoto, Kenji
在过去的十年里，人们对精神分裂症早期药物干预的潜在好处越来越感兴趣。精神分裂症患者在坦率的精神病发作前的几年内表现出非精神病性和非特异性的前驱症状(例如抑郁和认知障碍)。几项研究表明，在有前驱症状的人中使用非典型抗精神病药物可能会降低随后转变为精神分裂症的风险。此外，一项对有前驱症状的年轻人进行的自然主义治疗研究表明，服用抗抑郁药物可以防止精神病的发展。尽管这项研究的样本很小，但结果是惊人的。一些抗抑郁药物，包括选择性5-羟色胺再摄取抑制剂(SSRIs)，在内质网蛋白Sigma-1受体上具有高到中等的亲和力，这与神经保护和神经元可塑性有关。在所有抗抑郁药物中，氟伏沙明是最有效的sigma-1受体激动剂，因为选择性sigma-1受体拮抗剂NE-100能拮抗氟伏沙明的作用。基于Sigma-1受体在认知和抑郁的病理生理学中的作用，作者提出了一种假设，即SSRIs(例如，氟伏沙明)与Sigma-1受体激动剂一起使用可能会降低随后转变为精神分裂症的风险。
In the past decade there has been increasing interest in the potential benefit of early pharmacological intervention in schizophrenia. Patients with schizophrenia show nonpsychotic and nonspecific prodromal symptoms (e.g., depression and cognitive deficits) for several years preceding the onset of frank psychosis. Several studies have demonstrated that medication with atypical antipsychotic drugs in people with prodromal symptoms may reduce the risk of subsequent transition to schizophrenia. Furthermore, a naturalistic treatment study in young people with prodromal symptoms demonstrated that medication with antidepressants could prevent the development of psychosis. Although the sample in this study was small, the results were striking. Some antidepressants, including selective serotonin reuptake inhibitors (SSRIs), had high to moderate affinities at the endoplasmic reticulum protein sigma-1 receptors, which are implicated in neuroprotection and neuronal plasticity. Among all antidepressants, fluvoxamine was the most potent sigma-1 receptor agonist since the effects of fluvoxamine were antagonized by the selective sigma-1 receptor antagonist NE-100. Based on the role of sigma-1 receptors in the pathophysiology of cognition and depression, the author would like to propose a hypothesis that SSRIs (e. g., fluvoxamine) with sigma-1 receptor agonism may reduce the risk of subsequent transition to schizophrenia.