Biomedical Engineering Reference
In-Depth Information
Advances in Design and Development of Sodium
Channel Blockers
Valentina Zuliani, Laura Amori, and Mirko Rivara
Contents
1
Introduction: A Brief Mention of All Ion Channels .......................................
81
2 Sodium Channels: Their Structure and Functions, Diseases Related to Na-Channels . . .
82
2.1 VGSC Structure .......................................................................
82
2.2 VGSC Functions ......................................................................
83
2.3 VGSC
a
-Subunit Subtypes and Their Localization . . . ..............................
84
2.4 Diseases Related to VGSCs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
85
3 Advances in the Development of Sodium Channel Blockers:
A Few Introductory Lines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
3.1 As Antiepileptic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
3.2 As Pain-Relieving Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
3.3 For the Treatment of Other Diseases ................................................ 98
4 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
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 functional VGSC isoforms have been identified and have a distinct
pattern of expression within the human body. In addition, VGSC also have distinct
electrophysiological profiles with differing activation and inactivation states. As
