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The design and discovery of T-type calcium channel inhibitors for the treatment of central nervous system disorders. | LitMetric

The design and discovery of T-type calcium channel inhibitors for the treatment of central nervous system disorders.

Expert Opin Drug Discov

Korea Institute of Science and Technology, Future Convergence Research Division, Hwarangno 14-Gil 5, Seongbuk-Gu, Seoul 136-791, Republic of Korea.

Published: August 2013

AI Article Synopsis

Article Abstract

Introduction: 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.

Areas Covered: 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.

Expert Opinion: 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.

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Source
http://dx.doi.org/10.1517/17460441.2013.796926DOI Listing

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