title: The design and discovery of T-type calcium channel inhibitors for the treatment of central nervous system disorders.
abstract: BACKGROUND
  Neuronal T-type calcium channels (T-type channels) are expressed throughout the central nervous system (CNS), regulating neuronal excitability. T-type channels in the CNS are involved in various neurophysiological and pathophysiological states, and thus have become a promising therapeutic target.
  
  
  METHODS
  This article discusses T-type channel-related CNS disorders such as epilepsy, neuropathic pain, insomnia and tremor disorders including Parkinson's disease. In addition, the article reviews T-type channel inhibitors showing efficacy in animal models in such CNS disorders, with a focus on classical T-type channel inhibitors with limited specificity for T-type channels as well as novel inhibitors with high specificity. Furthermore, the article also presents and discusses the next generation of T-type channel inhibitor discovery, virtual as well as screening and high-throughput screening techniques.
  
  
  CONCLUSIONS
  Although T-type channel-related CNS disorders seem to be diverse, it converges into the one major cause - abnormal hyperactivity of neurons. T-type channel-specific inhibitors could thus be commonly applied for the treatment of such CNS disorders regardless of the complexity of individual disorder. Structural information of inhibitor-binding sites would facilitate the discovery of the next generation of T-type channel-specific inhibitors by stimulating structure-based rational drug designs.
authors: Korea Institute of Science and Technology, Future Convergence Research Division, Hwarangno 14-Gil 5, Seongbuk-Gu, Seoul 136-791, Republic of Korea. keehyun@kist.re.kr
authors: Kee-Hyun
authors: KH
authors: Choi
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D020747:Calcium Channels, T-Type / Q000502:physiology*; D002490:Central Nervous System / Q000502:physiology; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D055808:Drug Discovery; D006801:Humans
chemical_list: D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type