title: Block of Nav1.8 by small molecules.
abstract: Sodium channels are key proteins in regulating neuronal excitability and accumulating data suggest that specific subtypes of voltage-dependent sodium channels are important in signaling various types of pain. Consistent with this theme, Jarvis et al.(7) recently reported the identification of a subtype-selective Na(v)1.8 blocker that was active in several pre-clinical models of pain. During the course of these studies compounds were also identified that showed large differences in potency when tested on Na(v)1.8 channels from different species. This addendum illustrates one of these compounds along with the potency correlation between recombinant and native tetrodotoxin-resistant sodium channels for additional examples. These data show that significant differences can be observed for sodium channel blockers across species and highlight the importance of considering this possibility when searching for new compounds and research tools to probe sodium channel function.
authors.affiliation: Icagen, Inc., Durham, North Carolina 14487, USA. DKRAFTE@icagen.com
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Krafte
authors.forename: Mark
authors.initials: M
authors.lastname: Chapman
authors.forename: Brian
authors.initials: B
authors.lastname: Marron
authors.forename: Robert
authors.initials: R
authors.lastname: Atkinson
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.forename: Mark
authors.initials: M
authors.lastname: Curran
authors.forename: Michael
authors.initials: M
authors.lastname: Kort
authors.forename: Michael F
authors.initials: MF
authors.lastname: Jarvis
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D062559:NAV1.8 Voltage-Gated Sodium Channel; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D013045:Species Specificity
chemical_list: C520740:A 803467; D000700:Analgesics; D000814:Aniline Compounds; D005663:Furans; D062559:NAV1.8 Voltage-Gated Sodium Channel; D011994:Recombinant Proteins; C568317:SCN10A protein, human; D026941:Sodium Channel Blockers; D015222:Sodium Channels