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CorrectionCC BY V4.0, Open Access
Published VersionCC BY V4.0, Open Access
Journal article
Pharmacological characterisation of the highly Na v 1.7 selective spider venom peptide Pn3a
Scientific Reports, Vol.7, 40883
2017
Abstract
Human genetic studies have implicated the voltage-gated sodium channel Na V 1.7 as a therapeutic target for the treatment of pain. A novel peptide, μ-theraphotoxin-Pn3a, isolated from venom of the tarantula Pamphobeteus nigricolor, potently inhibits Na V 1.7 (IC 50 0.9 nM) with at least 40-1000-fold selectivity over all other Na V subtypes. Despite on-target activity in small-diameter dorsal root ganglia, spinal slices, and in a mouse model of pain induced by Na V 1.7 activation, Pn3a alone displayed no analgesic activity in formalin-, carrageenan- or FCA-induced pain in rodents when administered systemically. A broad lack of analgesic activity was also found for the selective Na V 1.7 inhibitors PF-04856264 and phlotoxin 1. However, when administered with subtherapeutic doses of opioids or the enkephalinase inhibitor thiorphan, these subtype-selective Na V 1.7 inhibitors produced profound analgesia. Our results suggest that in these inflammatory models, acute administration of peripherally restricted Na V 1.7 inhibitors can only produce analgesia when administered in combination with an opioid. © The Author(s) 2017.
Details
- Title
- Pharmacological characterisation of the highly Na v 1.7 selective spider venom peptide Pn3a
- Authors
- J R Deuis (Author) - University of QueenslandZ Dekan (Author) - University of QueenslandJ S Wingerd (Author) - University of QueenslandJ J Smith (Author) - University of QueenslandN R Munasinghe (Author) - University of SydneyR F Bhola (Author) - University of SydneyW L Imlach (Author) - University of SydneyVolker Herzig (Author) - University of QueenslandD A Armstrong (Author) - University of QueenslandK J Rosengren (Author)F Bosmans (Author)S G Waxman (Author)S D Dib-Hajj (Author)P Escoubas (Author)M S Minett (Author)M J Christie (Author)G F King (Author)P F Alewood (Author)R J Lewis (Author)J N Wood (Author)I Vetter (Author)
- Publication details
- Scientific Reports, Vol.7, 40883; 18
- Publisher
- Nature Publishing Group
- Date published
- 2017
- DOI
- 10.1038/srep40883
- ISSN
- 2045-2322
- Copyright note
- Copyright © The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
- Organisation Unit
- School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 99450952702621
- Output Type
- Journal article
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