Block of Nav1.8 by small molecules.
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.
Krafte
Douglas S
DS
Icagen, Inc., Durham, North Carolina 14487, USA. DKRAFTE@icagen.com
Chapman
Mark
M
Marron
Brian
B
Atkinson
Robert
R
Liu
Yi
Y
Ye
Fei
F
Curran
Mark
M
Kort
Michael
M
Jarvis
Michael F
MF
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
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