Latvian Institute of Organic Synthesis, Laboratory of Pharmaceutical Pharmacology, Aizkraukles 21, LV-1006 Riga, Latvia; University of Tartu, Faculty of Science and Technology, Institute of Chemistry, Ravila 14a, 50411 Tartu, Estonia.
Latvian Institute of Organic Synthesis, Laboratory of Pharmaceutical Pharmacology, Aizkraukles 21, LV-1006 Riga, Latvia.
Pharmacol Res. 2023 May;191:106771. doi: 10.1016/j.phrs.2023.106771. Epub 2023 Apr 15.
Over the last decade, sigma-1 receptor (Sig1R) has been recognized as a valid target for the treatment of seizure disorders and seizure-related comorbidities. Clinical trials with Sig1R ligands are underway testing therapies for the treatment of drug-resistant seizures, developmental and epileptic encephalopathies, and photosensitive epilepsy. However, the direct molecular mechanism by which Sig1R modulates seizures and the balance between excitatory and inhibitory pathways has not been fully elucidated. This review article aims to summarize existing knowledge of Sig1R and its involvement in seizures by focusing on the evidence obtained from Sig1R knockout animals and the anti-seizure effects of Sig1R ligands. In addition, this review article includes a discussion of the advantages and disadvantages of the use of existing compounds and describes the challenges and future perspectives on the use of Sig1R as a target for the treatment of seizure disorders.
在过去的十年中，sigma-1 受体 (Sig1R) 已被确认为治疗癫痫发作障碍和与癫痫发作相关的共病的有效靶点。正在进行针对 Sig1R 配体的临床试验，以测试治疗耐药性癫痫发作、发育性和癫痫性脑病以及光敏性癫痫的疗法。然而，Sig1R 调节癫痫发作的直接分子机制以及兴奋性和抑制性途径之间的平衡尚未完全阐明。本文综述的目的是通过重点关注 Sig1R 敲除动物获得的证据和 Sig1R 配体的抗癫痫作用，总结 Sig1R 及其在癫痫发作中的作用的现有知识。此外，本文还讨论了使用现有化合物的优缺点，并描述了将 Sig1R 作为治疗癫痫发作障碍的靶点的使用的挑战和未来展望。
