Skip to main content
placeholder image

Conotoxins targeting neuronal voltage-gated sodium channel subtypes: potential analgesics?

Journal Article


Download full-text (Open Access)

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.

Publication Date


  • 2012

Published In


Citation


  • Knapp, O., McArthur, J. R. & Adams, D. J. (2012). Conotoxins targeting neuronal voltage-gated sodium channel subtypes: potential analgesics?. Toxins, 4 (11), 1236-1260.

Scopus Eid


  • 2-s2.0-84870567345

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1625&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/603

Number Of Pages


  • 24

Start Page


  • 1236

End Page


  • 1260

Volume


  • 4

Issue


  • 11

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.

Publication Date


  • 2012

Published In


Citation


  • Knapp, O., McArthur, J. R. & Adams, D. J. (2012). Conotoxins targeting neuronal voltage-gated sodium channel subtypes: potential analgesics?. Toxins, 4 (11), 1236-1260.

Scopus Eid


  • 2-s2.0-84870567345

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1625&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/603

Number Of Pages


  • 24

Start Page


  • 1236

End Page


  • 1260

Volume


  • 4

Issue


  • 11