Recent Advances in the Medicinal Chemistry of Sodium Channel Blockers and their Therapeutic Potential

Authors: Zuliani, Valentina; Patel, Manoj K.; Fantini, Marco; Rivara, Mirko

Source: Current Topics in Medicinal Chemistry, Volume 9, Number 4, March 2009 , pp. 396-415(20)

Publisher: Bentham Science Publishers

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Abstract:

The voltage-gated sodium channels (VGSCs) play a fundamental role in controlling cellular excitability. Abnormal activity of sodium channels is related to several pathological processes, including cardiac arrhythmias, epilepsy, chronic pain, neurodegenerative diseases and spasticity. In view of this, VGSCs are considered important therapeutic targets for the treatment of these disorders. To date, nine VGSC isoforms have been identified and have a distinct pattern of expression within the human body. In addition, VGSCs also have distinct electrophysiological profiles with differing activation and inactivation states. As such, there is a concerted effort to develop not only isoform selective antagonists, but also antagonists that exhibit state selectivity, particularly to the inactivated state of the channel. This review will provide a brief historical prospective and will primarily focus on recent advances in the development of isoform specific and state selective sodium channel antagonists and the medicinal chemistry involved, surveying the emerging therapeutic fields.

Keywords: Sodium channels; blockers; Nav isoforms; pain; epilepsy

Document Type: Research article

DOI: http://dx.doi.org/10.2174/156802609788317856

Affiliations: 1: Dipartimento Farmaceutico, Universita degli Studi di Parma, V.le G.P. Usberti, 27/A, I-43100 Parma, Italy.

Publication date: 2009-03-01