Selective sigma-1 (sigma1) receptor antagonists: emerging target for the treatment of neuropathic pain.
Selective sigma-1 (sigma1) receptor antagonists: emerging target for the treatment of neuropathic pain.
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选择性 sigma-1 (sigma1) 受体拮抗剂：治疗神经性疼痛的新兴靶点。
DOI：
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发表时间：
2009
影响因子：
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通讯作者：
A. Torrens
中科院分区：
文献类型：
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作者：
J. Díaz;D. Zamanillo;J. Corbera;J. Baeyens;R. Maldonado;M. A. Pericàs;J. Vela;A. Torrens
目前已有大量研究提出了sigma(1)受体在非急性疼痛中的治疗作用，但对其在非急性疼痛中的作用尚未有很好的探讨。Sigma(1)受体敲除小鼠的出现为我们提供了研究Sigma(1)受体在伤害感觉中的作用的可能性，特别是在中枢致敏过程发挥重要作用的模型中。鉴于其诱人的治疗潜力，我们开发了一项旨在发现新型和选择性sigma(1)配体的化学计划。本文讨论了该方法的合理性基础，并报道了几种化学系列的初步药理结果及其对sigma(1)受体的构效关系。疼痛模型中的功能数据主要在一个系列中提出，该系列提供了证据，证明选择性sigma(1)受体拮抗剂是治疗神经性疼痛的创新和替代方法。
A large number of therapeutic roles have been proposed for sigma(1) receptors but the involvement of sigma(1) receptor in non-acute pain had not been well explored up to now. sigma(1) receptor knock-out mice became available offering us the possibility to study the role of sigma(1) receptor in nociception, particularly in models where central sensitization processes play a significant role. Given the attractive therapeutic potential, we have developed a chemical program aimed at the discovery of novel and selective sigma(1) ligands. Herein we discuss the rational basis of this approach and report preliminary pharmacological results of several chemical series and aspects of their structure-activity relationship on sigma(1) receptor. Functional data in pain models are presented mainly on one series that provide evidence to consider selective sigma(1) receptor antagonists an innovative and alternative approach for treating neuropathic pain.