Zahra Aqeela, Liu Ru, Wang Jingjing, Wu Jianping
Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, 122 Loushi Rd, Wuhan, 430070, China.
Department of Zoology, University of Sialkot, Sialkot, 51310, Pakistan.
Neurol Sci. 2023 Nov;44(11):3819-3825. doi: 10.1007/s10072-023-06955-x. Epub 2023 Jul 13.
Epilepsy is characterized by recurrent epileptic seizures caused by high levels of neuronal excitability in the brain. Voltage-sensitive K+ channels (Kv) of the Kv7 (KCNQ) family encoded by the KCNQ gene are involved in a wide range of cellular processes, i.e., KCNQ2 and KCNQ3 channels mediate M-currents to inhibit neuronal excitability and reduce transmitter release throughout the nervous system. Thus, as a positive allosteric modulator (or opener) of KCNQ channels, retigabine has been the only clinically approved anti-seizure medication that acts on the KCNQ channels. This review discusses the biochemical mechanisms about how retigabine acts on Kv7 channels, significance in neuronal pathophysiology, preclinical efficacy, and clinical stage of development. Additional efforts are being made to emphasize the possible benefits and drawbacks of retigabine compared to currently available medications for treatment-resistant epilepsy.
癫痫的特征是由大脑中高水平的神经元兴奋性引起的反复发作的癫痫发作。由KCNQ基因编码的Kv7（KCNQ）家族的电压敏感性钾通道（Kv）参与广泛的细胞过程，即KCNQ2和KCNQ3通道介导M电流以抑制神经元兴奋性并减少整个神经系统中的递质释放。因此，作为KCNQ通道的正变构调节剂（或开放剂），瑞替加滨一直是唯一临床上批准的作用于KCNQ通道的抗癫痫药物。本综述讨论了瑞替加滨作用于Kv7通道的生化机制、在神经元病理生理学中的意义、临床前疗效以及临床开发阶段。此外，还强调了与目前用于治疗难治性癫痫的药物相比，瑞替加滨可能的益处和缺点。
