title: N-type calcium channel blockers: novel therapeutics for the treatment of pain.
abstract: Highly selective Ca(v)2.2 voltage-gated calcium channel (VGCC) inhibitors have emerged as a new class of therapeutics for the treatment of chronic and neuropathic pain. Cone snail venoms provided the first drug in class with FDA approval granted in 2005 to Prialt (omega-conotoxin MVIIA, Elan) for the treatment of neuropathic pain. Since this pioneering work, major efforts underway to develop alternative small molecule inhibitors of Ca(v)2.2 calcium channel have met with varied success. This review focuses on the properties of the Ca(v)2.2 calcium channel in different pain states, the action of omega-conotoxins GVIA, MVIIA and CVID, describing their structure-activity relationships and potential as leads for the design of improved Ca(v)2.2 calcium channel therapeutics, and finally the development of small molecules for the treatment of chronic pain.
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: C I
authors.initials: CI
authors.lastname: Schroeder
authors.forename: C J
authors.initials: CJ
authors.lastname: Doering
authors.forename: G W
authors.initials: GW
authors.lastname: Zamponi
authors.forename: R J
authors.initials: RJ
authors.lastname: Lewis
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D006801:Humans; D010146:Pain / Q000188:drug therapy*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D010455:Peptides; D021122:Protein Subunits