Small molecules targeting sodium and calcium channels for neuropathic pain.
Neuropathic pain is a chronic disease, which impacts millions of individuals worldwide. The condition is currently treated with several drugs that provide pain relief that is inconsistent and complicated by CNS or cardiovascular (CV) side effects. Voltage-gated sodium channels (VGSCs) and voltage-gated calcium channels (VGCCs) are of particular interest as targets for neuropathic pain because they control electrical signals in both the central and peripheral nervous system. Recent research has demonstrated that the expression of voltage-gated ion channels changes significantly under conditions of neuropathic pain in rodents and humans. Selective modulation of the channels involved in the pathology of the disease, while sparing the channels that are essential for normal nociception, offers promising opportunities for therapeutic intervention. This review summarizes recent developments of small molecules that target VGSCs and VGCCs.
Bear
Brian
B
Vertex Pharmaceuticals San Diego, San Diego, CA 92121, USA. brian_bear@sd.vrtx.com
Asgian
Juliana
J
Termin
Andreas
A
Zimmermann
Nicole
N
D000818:Animals; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015220:Calcium Channels / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D062556:NAV1.7 Voltage-Gated Sodium Channel; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D026941:Sodium Channel Blockers / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015222:Sodium Channels / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D062556:NAV1.7 Voltage-Gated Sodium Channel; D062559:NAV1.8 Voltage-Gated Sodium Channel; C568317:SCN10A protein, human; C486866:SCN9A protein, human; D054852:Small Molecule Libraries; D026941:Sodium Channel Blockers; D015222:Sodium Channels