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Review Article

电压门控钙通道α2δ亚基配体治疗慢性神经性疼痛的研究进展及药效模拟对结构-活性关系（SAR）的见解

卷 29, 期 30, 2022

发表于: 15 June, 2022

页: [5097 - 5112] 页: 16

弟呕挨: 10.2174/0929867329666220407093727

价格: $65

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摘要

背景：神经性疼痛（NP）是与神经损伤有关的复杂症状。治疗慢性NP的新药的发现已经持续了几十年，而由于目前可用药物的疗效和副作用，仍需要更多的进展。在所有已批准的慢性NP药物中，电压门控钙通道（VGCC）α2δ亚基配体（也称为加巴喷丁类药物）是一线治疗药物之一，代表了一类有效且相对安全的治疗药物。然而，由于答复率不尽如人意，仍需探索新的战略。 目的：本研究旨在通过涵盖上市和临床前/临床研究，综述加巴喷丁类药物治疗慢性NP的发现和开发的最新进展。此外，它旨在分析加巴喷丁类化合物的结构 - 活性关系（SAR），以促进未来设计靶向VGCC α2δ亚基的结构新型治疗剂。 方法：检索PubMed Central、Embase、Cochrane图书馆、科学网、Scopus和Espacenet，寻找从早期到2021年6月10日糖尿病周围神经性疼痛、带状疱疹后神经痛、纤维肌痛、电压门控钙通道α2δ亚基和相关治疗药物的文献和专利。加巴喷丁类化合物的SAR通过使用薛定谔套件中的相模块通过药效团建模进行分析。 结果：多种加巴喷丁类化合物被鉴定为VGCC α2δ配体，这些配体一直在开发中以治疗慢性NP。其中，四种加巴喷丁类药物上市，一种处于活跃的晚期临床试验中，八种已经停产。使用薛定谔套件中的相模块生成药效团模型，并根据药效特征预测常见药效团并进行分析。 结论：综述了加巴喷丁类药物治疗慢性NP的最新进展。此外，通过药效团建模分析了加巴喷丁类药物的结构-活性关系（SAR），这对于未来设计靶向VGCC α2δ亚基的结构新型治疗剂具有重要意义。

关键词: 电压门控钙通道，α2δ亚基，神经性疼痛，结构 - 活性关系（SAR），药效团建模，加巴喷丁类化合物。

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