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具有新型靶点的新型抗癫痫药物研发的最新进展

Recent Progress in the Development of New Antiepileptic Drugs with Novel Targets.

作者信息

Belete Tafere Mulaw

机构信息

Department of Pharmacology, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia, Africa.

出版信息

Ann Neurosci. 2023 Oct;30(4):262-276. doi: 10.1177/09727531231185991. Epub 2023 Aug 17.

Abstract

BACKGROUND

Epilepsy is a chronic neurological disorder that affects approximately 50-70 million people worldwide. Epilepsy has a significant economic and social burden on patients as well as on the country. The recurrent, spontaneous seizure activity caused by abnormal neuronal firing in the brain is a hallmark of epilepsy. The current antiepileptic drugs provide symptomatic relief by restoring the balance of excitatory and inhibitory neurotransmitters. Besides, about 30% of epileptic patients do not achieve seizure control. The prevalence of adverse drug reactions, including aggression, agitation, irritability, and associated comorbidities, is also prevalent. Therefore, researchers should focus on developing more effective, safe, and disease-modifying agents based on new molecular targets and signaling cascades.

SUMMARY

This review overviews several clinical trials that help identify promising new targets like lactate dehydrogenase inhibitors, c-jun n-terminal kinases, high mobility group box-1 antibodies, astrocyte reactivity inhibitors, cholesterol 24-hydroxylase inhibitors, glycogen synthase kinase-3 beta inhibitors, and glycolytic inhibitors to develop a new antiepileptic drug.

KEY MESSAGES

Approximately 30% of epileptic patients do not achieve seizure control. The current anti-seizure drugs are not disease modifying, cure or prevent epilepsy. Lactate dehydrogenase inhibitor, cholesterol 24-hydroxylase inhibitor, glycogen synthase kinase-3 beta inhibitors, and mTOR inhibitors have a promising antiepileptogenic effect.

摘要

背景

癫痫是一种慢性神经系统疾病,全球约有5000万至7000万人受其影响。癫痫给患者以及国家带来了巨大的经济和社会负担。大脑中异常神经元放电引起的反复自发性癫痫发作活动是癫痫的一个标志。目前的抗癫痫药物通过恢复兴奋性和抑制性神经递质的平衡来提供症状缓解。此外,约30%的癫痫患者无法实现癫痫发作控制。包括攻击性、激越、易怒以及相关合并症在内的药物不良反应也很普遍。因此,研究人员应专注于基于新的分子靶点和信号级联开发更有效、安全且能改变疾病进程的药物。

总结

本综述概述了几项有助于确定有前景的新靶点的临床试验,如乳酸脱氢酶抑制剂、c-jun氨基末端激酶、高迁移率族蛋白B1抗体、星形胶质细胞反应性抑制剂、胆固醇24-羟化酶抑制剂、糖原合酶激酶-3β抑制剂和糖酵解抑制剂,以开发新型抗癫痫药物。

关键信息

约30%的癫痫患者无法实现癫痫发作控制。目前的抗癫痫药物不能改变疾病进程、治愈或预防癫痫。乳酸脱氢酶抑制剂、胆固醇24-羟化酶抑制剂、糖原合酶激酶-3β抑制剂和mTOR抑制剂具有有前景的抗癫痫发生作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/10662271/0c4cd2c4dff9/10.1177_09727531231185991-fig1.jpg

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