Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland.
Curr Med Chem. 2013;20(10):1241-85. doi: 10.2174/0929867311320100005.
Ion channel targeted drugs have always been related with either the central nervous system (CNS), the peripheral nervous system, or the cardiovascular system. Within the CNS, basic indications of drugs are: sleep disorders, anxiety, epilepsy, pain, etc. However, traditional channel blockers have multiple adverse events, mainly due to low specificity of mechanism of action. Lately, novel ion channel subtypes have been discovered, which gives premises to drug discovery process led towards specific channel subtypes. An example is Na(+) channels, whose subtypes 1.3 and 1.7-1.9 are responsible for pain, and 1.1 and 1.2 - for epilepsy. Moreover, new drug candidates have been recognized. This review is focusing on ion channels subtypes, which play a significant role in current drug discovery and development process. The knowledge on channel subtypes has developed rapidly, giving new nomenclatures of ion channels. For example, Ca(2+)s channels are not any more divided to T, L, N, P/Q, and R, but they are described as Ca(v)1.1-Ca(v)3.3, with even newer nomenclature α1A-α1I and α1S. Moreover, new channels such as P2X1-P2X7, as well as TRPA1-TRPV1 have been discovered, giving premises for new types of analgesic drugs.
靶向离子通道的药物一直与中枢神经系统（CNS）、周围神经系统或心血管系统有关。在中枢神经系统中，药物的基本适应症是：睡眠障碍、焦虑、癫痫、疼痛等。然而，传统的通道阻滞剂有多种不良反应，主要是由于作用机制的特异性低。最近，发现了新型的离子通道亚型，为针对特定通道亚型的药物发现过程提供了前提。例如，钠离子通道的亚型 1.3 和 1.7-1.9 负责疼痛，而 1.1 和 1.2 则负责癫痫。此外，还发现了新的药物候选物。本综述重点介绍在当前药物发现和开发过程中起重要作用的离子通道亚型。通道亚型的知识发展迅速，赋予了离子通道新的命名法。例如，钙通道不再分为 T、L、N、P/Q 和 R，而是被描述为 Ca(v)1.1-Ca(v)3.3，甚至有更新的命名法，如α1A-α1I 和α1S。此外，还发现了新的通道，如 P2X1-P2X7，以及 TRPA1-TRPV1，为新型的镇痛药物提供了前提。
