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布美他尼对儿童和青少年自闭症谱系障碍的治疗效果:一项综述研究。

Bumetanide Therapeutic Effect in Children and Adolescents With Autism Spectrum Disorder: A Review Study.

作者信息

Mollajani Raheleh, Joghataei Mohamad Taghi, Tehrani-Doost Mehdi

机构信息

Cognitive Neuroscience Institute for Cognitive Science Studies, Tehran, Iran.

Department of Anatomy and Neuroscience, Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.

出版信息

Basic Clin Neurosci. 2019 Sep-Oct;10(5):433-441. doi: 10.32598/bcn.9.10.380. Epub 2019 Sep 1.

Abstract

INTRODUCTION

Autism Spectrum Disorder (ASD) is characterized by several impairments in communications and social interactions, as well as restricted interests or stereotyped behaviors. Interventions applied for this disorder are based on multi-modal approaches, including pharmacotherapy. No definitive cure or medication has been introduced so far; therefore, researchers still investigate potential drugs for treating ASD. One of the new medications introduced for this purpose is bumetanide. The present article aimed to review the efficacy of this drug on the core symptoms of ASD and its potential side effects.

METHODS

We searched all papers reported on pharmacokinetics, pharmacodynamics, efficacy, and adverse effects of bumetanide on animal models and humans with ASD. The papers were extracted from the main databases of PubMed, Web of Science, and Scopus.

RESULTS

The findings revealed that cortical neurons have high Chloride ion (Cl-)i and excitatory actions of gamma-aminobutyric acid in the valproic acid animal model with ASD and mice with fragile X syndrome. Bumetanide, which has been introduced as a diuretic, is also a high-affinity-specific Na+-K+-Cl- cotransporter (NKCC1) antagonist that can reduce Cl- level. The results also indicate that bumetanide can attenuate behavioral features of autism in both animal and human models. Moreover, the studies showed that such medication could activate fusiform face area in individuals with ASD while viewing emotional faces. Also, recent findings suggest that a dose of 1 mg/d of this drug, taken twice daily, might be the best compromise between safety and efficacy.

CONCLUSION

Recent studies provided some evidence that bumetanide can be a novel pharmacological agent in treating core symptoms of ASD. Future studies are required to confirm the efficacy of this medication in individuals with ASD.

摘要

引言

自闭症谱系障碍(ASD)的特征是在沟通和社交互动方面存在多种障碍,以及兴趣受限或行为刻板。针对这种疾病的干预措施基于多模式方法,包括药物治疗。迄今为止,尚未有明确的治愈方法或药物;因此,研究人员仍在研究治疗ASD的潜在药物。为此引入的一种新药是布美他尼。本文旨在综述该药对ASD核心症状的疗效及其潜在副作用。

方法

我们检索了所有关于布美他尼在动物模型和ASD患者中的药代动力学、药效学、疗效和不良反应的报告论文。这些论文从PubMed、科学网和Scopus等主要数据库中提取。

结果

研究结果显示,在丙戊酸诱导的ASD动物模型和脆性X综合征小鼠中,皮质神经元具有高浓度的细胞内氯离子(Cl-)i,且γ-氨基丁酸具有兴奋性作用。作为利尿剂引入的布美他尼也是一种高亲和力特异性钠-钾-氯共转运体(NKCC1)拮抗剂,可降低Cl-水平。结果还表明,布美他尼可减轻动物和人类模型中的自闭症行为特征。此外,研究表明,这种药物在ASD个体观看情感面孔时可激活梭状回面孔区。最近的研究结果还表明,每天服用1毫克、分两次服用的剂量可能是安全性和疗效之间的最佳折衷方案。

结论

最近的研究提供了一些证据,表明布美他尼可能是治疗ASD核心症状的新型药物。未来需要进一步研究以证实该药对ASD患者的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b14/7149950/f6760a69d4f4/BCN-10-433-g001.jpg

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