title: Conotoxins targeting neuronal voltage-gated sodium channel subtypes: potential analgesics?
abstract: Voltage-gated sodium channels (VGSC) are the primary mediators of electrical signal amplification and propagation in excitable cells. VGSC subtypes are diverse, with different biophysical and pharmacological properties, and varied tissue distribution. Altered VGSC expression and/or increased VGSC activity in sensory neurons is characteristic of inflammatory and neuropathic pain states. Therefore, VGSC modulators could be used in prospective analgesic compounds. VGSCs have specific binding sites for four conotoxin families: μ-, μO-, δ- and ί-conotoxins. Various studies have identified that the binding site of these peptide toxins is restricted to well-defined areas or domains. To date, only the μ- and μO-family exhibit analgesic properties in animal pain models. This review will focus on conotoxins from the μ- and μO-families that act on neuronal VGSCs. Examples of how these conotoxins target various pharmacologically important neuronal ion channels, as well as potential problems with the development of drugs from conotoxins, will be discussed.
authors.affiliation: Health Innovations Research Institute, RMIT University, Melbourne, Victoria 3083, Australia. oliver.knapp@rmit.edu.au
authors.forename: Oliver
authors.initials: O
authors.lastname: Knapp
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: McArthur
authors.forename: David J
authors.initials: DJ
authors.lastname: Adams
mesh_terms: D000595:Amino Acid Sequence; D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001665:Binding Sites; D020916:Conotoxins / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D052078:Conus Snail / Q000187:drug effects / Q000378:metabolism; D055808:Drug Discovery; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D061567:Voltage-Gated Sodium Channel Blockers / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism
chemical_list: D000700:Analgesics; D020916:Conotoxins; D061567:Voltage-Gated Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels