Department of Clinical Neurosciences, Faculty of Medicine, Foothills Medical Centre, Calgary MS Clinic, University of Calgary, Calgary, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.
CNS Neurosci Ther. 2013 Oct;19(10):737-44. doi: 10.1111/cns.12154. Epub 2013 Jul 22.
Multiple sclerosis (MS) is a central nervous system disorder that is associated with progressive oligodendrocyte and neuronal loss, axonal degeneration, and demyelination. Several medications that mitigate immune abnormalities reduce both the frequency of relapses and inflammation on magnetic resonance imaging, leading to improved outcomes for people with the relapsing-remitting form of MS. However, there are no treatments for the progressive forms of MS where neurons and axons continue to degenerate; here, neuroprotective therapies, or medications that rebuild myelin to confer axonal well-being, may be useful. Quetiapine fumarate is an atypical antipsychotic with reported remyelinating and neuroprotective properties in inflammatory and noninflammatory models of demyelination, including experimental autoimmune encephalomyelitis, and both cuprizone- and global cerebral ischemia-induced demyelination. Preclinical studies suggest that quetiapine may exert these effects by stimulating proliferation and maturation of oligodendrocytes, releasing neurotrophic factors, increasing antioxidant defences, scavenging for free radicals, and inhibiting activated microglia, astrocytes, and T lymphocytes. Additionally, quetiapine may be beneficial for psychiatric and nonpsychiatric symptoms of MS including depression, anxiety, insomnia, and possibly even pain. These data indicate that clinical trials are justified to determine the safety, tolerability, and efficacy of quetiapine fumarate in MS.
多发性硬化症(MS)是一种中枢神经系统疾病,与少突胶质细胞和神经元的进行性丧失、轴突变性和脱髓鞘有关。几种减轻免疫异常的药物可降低复发频率和磁共振成像上的炎症,从而改善复发缓解型 MS 患者的预后。然而,对于神经元和轴突继续退化的进行性 MS 形式,没有治疗方法;在这里,神经保护疗法或重建髓鞘以赋予轴突健康的药物可能是有用的。富马酸喹硫平是一种非典型抗精神病药,在炎症和非炎症性脱髓鞘模型中具有报道的髓鞘再生和神经保护特性,包括实验性自身免疫性脑脊髓炎,以及杯状醇和全脑缺血诱导的脱髓鞘。临床前研究表明,喹硫平可能通过刺激少突胶质细胞的增殖和成熟、释放神经营养因子、增加抗氧化防御、清除自由基以及抑制激活的小胶质细胞、星形胶质细胞和 T 淋巴细胞来发挥这些作用。此外,喹硫平可能对 MS 的精神和非精神症状有益,包括抑郁、焦虑、失眠,甚至可能还有疼痛。这些数据表明,有理由进行临床试验,以确定富马酸喹硫平在 MS 中的安全性、耐受性和疗效。