Department of Neurology, Great Ormond Street Hospital for Children NHS Trust, London, UK.
Developmental Neurosciences, University College London NIHR BRC Great Ormond Street Institute of Child Health, London, UK.
Dev Med Child Neurol. 2021 Aug;63(8):899-907. doi: 10.1111/dmcn.14822. Epub 2021 Feb 9.
Fenfluramine hydrochloride has classically been described as acting pharmacologically through a serotonergic mechanism. Therefore, it was initially used as an anorectic drug, given that impaired serotonin homeostasis may be associated with increased food intake. Although positive results were documented, cardiovascular concerns resulted in its temporary withdrawal. Nevertheless, a novel role in patients with epilepsy was later suggested by isolated clinical observations. The wide application of genetic testing allowed the classification (predominantly as Dravet syndrome) of patients in whom benefit was seen, while with the development of zebrafish models, its antiepileptic properties were confirmed at a molecular level. Data from randomized clinical trials have shown a beneficial effect of fenfluramine, as an adjunct therapy, on seizure control for children with Dravet syndrome, though there is still uncertainty about the impact on neurodevelopment in these patients. No signs of heart valve disease have been documented to date. Long-term and appropriately designed clinical studies will verify whether fenfluramine is a therapeutic agent of high importance, living up to the promise shown so far. What this paper adds Fenfluramine is a very promising repurposed therapy specifically for seizures in Dravet syndrome. The long-term effect of fenfluramine on neurodevelopmental prognosis requires further investigation.
盐酸芬氟拉明经典地被描述为通过 5-羟色胺能机制发挥药理学作用。因此，它最初被用作减肥药，因为 5-羟色胺稳态的损害可能与食物摄入增加有关。尽管有阳性结果的记录，但心血管方面的考虑导致其暂时撤出。然而，后来通过孤立的临床观察提示了其在癫痫患者中的新作用。基因检测的广泛应用允许对受益患者进行分类（主要为 Dravet 综合征），而随着斑马鱼模型的发展，其在分子水平上的抗癫痫特性得到了证实。随机临床试验的数据表明，芬氟拉明作为辅助治疗对 Dravet 综合征儿童的癫痫发作控制有有益的效果，尽管对于这些患者的神经发育的影响仍存在不确定性。迄今为止，尚未记录到心脏瓣膜疾病的迹象。长期和适当设计的临床研究将验证芬氟拉明是否是一种具有高度重要性的治疗药物，是否符合迄今为止的表现。本文的新内容芬氟拉明是一种非常有前途的重新定位疗法，特别是针对 Dravet 综合征的癫痫发作。芬氟拉明对神经发育预后的长期影响需要进一步研究。
