Ion Channels as Drug Targets in Central Nervous System Disorders

被引:23
作者
Waszkielewicz, A. M. [1 ]
Gunia, A. [1 ]
Szkaradek, N. [1 ]
Sloczynska, K. [1 ]
Krupinska, S. [1 ]
Marona, H. [1 ]
机构
[1] Jagiellonian Univ, Fac Pharm, Coll Med, Dept Bioorgan Chem,Chair Organ Chem, PL-30688 Krakow, Poland
关键词
ASIC; central nervous system; CNS; KCNQ; ion channels; NMDA; P2X; TRP; GATED SODIUM-CHANNELS; D-ASPARTATE RECEPTOR; TARANTULA TOXIN PSALMOTOXIN-1; PERIPHERAL NEUROPATHIC PAIN; GLYCINE ANTAGONIST GV150526; ACID-SENSING ION-CHANNEL-1; SUBTYPE-SELECTIVE AGONIST; TRAUMATIC BRAIN-INJURY; TRANSGENIC MOUSE MODEL; ISCHEMIC CELL-DEATH;
D O I
暂无
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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, Ca2+ 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 alpha 1A-alpha 1I and alpha 1S. Moreover, new channels such as P2X1-P2X7, as well as TRPA1-TRPV1 have been discovered, giving premises for new types of analgesic drugs.
引用
收藏
页码:1241 / 1285
页数:45
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