Dipartimento Farmaceutico, Università degli Studi di Parma, V.le G.P. Usberti 27/A, I-43124 Parma, Italy.
Expert Opin Ther Pat. 2010 Jun;20(6):755-79. doi: 10.1517/13543771003774118.
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.
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.
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.
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.
电压门控钠离子通道（VGSCs）在控制细胞兴奋性方面起着至关重要的作用，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（例如疱疹后和三叉神经痛、糖尿病性神经病和脊髓损伤）是一个严重的临床问题，影响了世界上很大一部分人口。由于改变的钠通道同工型表达谱被认为是神经元兴奋性变化的一个原因，因此一直在寻找新的选择性靶向钠通道的分子来治疗慢性疼痛。
本综述使用 PubMed、http://www.sciencedirect.com/ 、SciFinder Scholar 和 http://ep.espacenet.com/ 作为资源，考虑了 2007 年至 2009 年 9 月之间的专利，对本文综述和讨论的钠通道阻滞剂分子类别进行了综述。
根据其广泛的结构多样性，本文报道的钠通道阻滞剂已被分类为不同的分子类别。这种分类有些任意，不一定反映出药效团元素的存在，但为讨论和评论最近专利的结构同系物类化学型提供了一种有用的方法。
近年来，专利申请数量不断增加，以及目前处于临床开发阶段的化合物数量不断增加，突显了钠通道阻滞剂领域的持续发现，这表明该靶点在治疗神经性疼痛方面的重要性。设计新的选择性和活性结构的巨大困难，这些结构无法从通常与高不良反应风险相关的旧 VGSC 阻滞剂中获得，这是对药物化学研究的一个巨大挑战。
