Strategies to identify ion channel modulators: current and novel approaches to target neuropathic pain.
Modulation of ion channel function has been a successful area for drug development, with ion channel modulating drugs being used in the therapeutic treatment of epilepsy, hypertension, diabetes and chronic pain. Most of the ion channel-modulating drugs that are currently on the market were developed without extensive knowledge of the molecular structure of ion channels, or an understanding of the full complexity of ion channel subtypes or knowledge of how ion channel expression is regulated during pathology. As new information on the roles that different ion channel subtypes play in pathophysiological processes becomes available, drugs will be designed to target specific ion channel subtypes via mechanisms that involve either direct channel block or modulation of ion channel functional expression. Using neuropathic pain as an example, this article reviews current knowledge of the structure and function of ion channels and current technology and future opportunities for the identification of novel drugs that are capable of modulating ion channel function.
Birch
Phillip J
PJ
Ionix Pharmaceuticals, 418 Cambridge Science Park, Cambridge, UK CB4 0PA. pbirch@ionixpharma.co
Dekker
Lodewijk V
LV
James
Iain F
IF
Southan
Andrew
A
Cronk
David
D
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D005456:Fluorescent Dyes; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship
D015220:Calcium Channels; D005456:Fluorescent Dyes; D007473:Ion Channels; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568317:SCN10A protein, human; D015222:Sodium Channels