Sodium channel blockers for neuropathic pain
Sodium channel blockers for neuropathic pain
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DOI：
10.1517/13543771003774118
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发表时间：
2010-05
影响因子：
6.6
通讯作者：
V. Zuliani;Mirko Rivara;Marco Fantini;G. Costantino
中科院分区：
文献类型：
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作者：
V. Zuliani;Mirko Rivara;Marco Fantini;G. Costantino
该领域的重要性：电压门控钠通道（VGSC）在控制细胞兴奋性方面发挥着重要作用，其异常活动与多种病理过程有关，包括心律失常、癫痫、神经退行性疾病、痉挛、慢性和神经性疼痛。特别是，神经性疼痛（例如，带状疱疹后神经痛和三叉神经痛、糖尿病性神经病变和脊髓损伤）是影响世界很大比例人口的严重临床问题。由于钠通道亚型表达谱的改变被认为是神经元兴奋性变化的原因之一，因此人们不断寻求针对钠通道的新选择性分子来治疗慢性疼痛。本综述涵盖的领域：PubMed、http://www.sciencedirect.com/、SciFinder® Scholar 和 http://ep.espacenet.com/ 被用作本综述的来源，并且将 2007 年至 2009 年 9 月期间的专利考虑到本文综述和讨论的钠通道阻滞剂分子类别。读者将获得什么：本综述中报道的钠通道阻滞剂根据其广泛的结构多样性被分为不同的分子类别。这种分类有些随意，不一定反映药效基团元素的存在，但提供了一种有用的方法来讨论和评论最近获得专利的化学型的结构同质类别。主要信息：钠通道阻滞剂领域的不断发现，特别是过去几年发布的专利申请数量不断增加以及目前处于临床开发中的化合物数量不断增加，强调了该靶点对于治疗神经性疼痛的重要性。设计新的选择性和活性结构的巨大困难是药物化学研究面临的巨大挑战，而旧的 VGSC 阻断剂往往与高风险的不良反应相关。
Importance of the field: The voltage-gated sodium channels (VGSCs) play a fundamental role in controlling cellular excitability and their abnormal activity is related to several pathological processes, including cardiac arrhythmias, epilepsy, neurodegenerative diseases, spasticity, chronic and neuropathic pain. In particular, neuropathic pain (e.g., postherpetic and trigeminal neuralgia, diabetic neuropathy and spinal cord injury) is a serious clinical problem that affects a high percentage of the world population. Because an altered sodium channel isoform expression profile has been considered one reason for the changes in neuronal excitability, there is a continuous quest for new selective molecules targeting sodium channels for the treatment of chronic pain. Areas covered in this review: PubMed, http://www.sciencedirect.com/, SciFinder® Scholar and http://ep.espacenet.com/ were used as sources for this review and patents between 2007 and September 2009 were taken into account for the sodium channel blockers molecular classes reviewed and discussed herein. What the reader will gain: The sodium channel blockers reported in this review have been categorized into different molecular classes on the basis of their wide structural diversity. This classification, somewhat arbitrary, does not necessarily reflect the presence of pharmacophoric elements but offers a useful way to discuss and comment on structurally homogenous classes of chemotypes recently patented. Take home message: The continuous discoveries in the field of sodium channel blockers, highlighted by the increasing numbers of patent applications published in the last few years and by the numbers of compounds currently in clinical development, underline the importance of this target for the treatment of neuropathic pain. The great difficulty in the design of new selective and active structures, not obtained from old VGSC blockers that are often associated with high risk of adverse effects, is a strong challenge for medicinal chemistry research.