Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College in Kraków, PL 30-688 Kraków, Poland.
Int J Mol Sci. 2023 Jan 18;24(3):1908. doi: 10.3390/ijms24031908.
Since the 1990s, ionotropic glutamate receptors have served as an outstanding target for drug discovery research aimed at the discovery of new neurotherapeutic agents. With the recent approval of perampanel, the first marketed non-competitive antagonist of AMPA receptors, particular interest has been directed toward 'non-NMDA' (AMPA and kainate) receptor inhibitors. Although the role of AMPA receptors in the development of neurological or psychiatric disorders has been well recognized and characterized, progress in understanding the function of kainate receptors (KARs) has been hampered, mainly due to the lack of specific and selective pharmacological tools. The latest findings in the biology of KA receptors indicate that they are involved in neurophysiological activity and play an important role in both health and disease, including conditions such as anxiety, schizophrenia, epilepsy, neuropathic pain, and migraine. Therefore, we reviewed recent advances in the field of competitive and non-competitive kainate receptor antagonists and their potential therapeutic applications. Due to the high level of structural divergence among the compounds described here, we decided to divide them into seven groups according to their overall structure, presenting a total of 72 active compounds.
自 20 世纪 90 年代以来，离子型谷氨酸受体已成为药物发现研究的一个突出靶点，旨在发现新的神经治疗药物。随着最近批准的苯丙胺，即第一个上市的 AMPA 受体非竞争性拮抗剂，人们对“非-NMDA”（AMPA 和 kainate）受体抑制剂特别感兴趣。尽管 AMPA 受体在神经或精神疾病的发展中的作用已得到充分认识和描述，但对 kainate 受体 (KARs) 的功能的理解进展却受到阻碍，主要是由于缺乏特异性和选择性的药理学工具。KA 受体生物学的最新发现表明，它们参与神经生理活动，在健康和疾病中都发挥着重要作用，包括焦虑、精神分裂症、癫痫、神经病理性疼痛和偏头痛等疾病。因此，我们综述了竞争性和非竞争性 kainate 受体拮抗剂及其潜在治疗应用的最新进展。由于这里描述的化合物在结构上有很大的差异，我们决定根据它们的整体结构将它们分为七个组，总共展示了 72 种活性化合物。
