Díaz José Luis, Zamanillo Daniel, Corbera Jordi, Baeyens José Manuel, Maldonado Rafael, Pericàs Miquel Angel, Vela José Miguel, Torrens Antoni
Department of Chemistry, ESTEVE, Av. Mare de Déu de Montserrat 221, 08041 Barcelona, Spain.
Cent Nerv Syst Agents Med Chem. 2009 Sep;9(3):172-83. doi: 10.2174/1871524910909030172.
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.
西格玛-1受体已被提出具有多种治疗作用，但迄今为止，西格玛-1受体在非急性疼痛中的作用尚未得到充分研究。西格玛-1受体基因敲除小鼠的出现，为我们研究西格玛-1受体在伤害感受中的作用提供了可能，特别是在中枢敏化过程起重要作用的模型中。鉴于其诱人的治疗潜力，我们开展了一个化学项目，旨在发现新型选择性西格玛-1配体。在此，我们讨论这种方法的理论基础，并报告几个化学系列的初步药理学结果及其与西格玛-1受体的构效关系。疼痛模型中的功能数据主要针对一个系列呈现，这些数据为将选择性西格玛-1受体拮抗剂视为治疗神经性疼痛的创新替代方法提供了证据。
