Targeting voltage-gated calcium channels: developments in peptide and small-molecule inhibitors for the treatment of neuropathic pain

Vink, S. and Alewood, P. F. (2012) Targeting voltage-gated calcium channels: developments in peptide and small-molecule inhibitors for the treatment of neuropathic pain. British Journal of Pharmacology, 167 5: 970-989. doi:10.1111/j.1476-5381.2012.02082.x


Author Vink, S.
Alewood, P. F.
Title Targeting voltage-gated calcium channels: developments in peptide and small-molecule inhibitors for the treatment of neuropathic pain
Journal name British Journal of Pharmacology   Check publisher's open access policy
ISSN 0007-1188
1476-5381
Publication date 2012-11
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1111/j.1476-5381.2012.02082.x
Volume 167
Issue 5
Start page 970
End page 989
Total pages 20
Place of publication Chichester, West Sussex, United Kingdom
Publisher John Wiley & Sons
Collection year 2013
Language eng
Formatted abstract
Chronic pain affects approximately 20% of people worldwide and places a large economic and social burden on society. Despite the availability of a range of analgesics, this condition is inadequately treated, with complete alleviation of symptoms rarely occurring. In the past 30 years, the voltage-gated calcium channels (VGCCs) have been recognized as potential targets for analgesic development. Although the majority of the research has been focused on Cav2.2 in particular, other VGCC subtypes such as Cav3.2 have recently come to the forefront of analgesic research. Venom peptides from marine cone snails have been proven to be a valuable tool in neuroscience, playing a major role in the identification and characterization of VGCC subtypes and producing the first conotoxin-based drug on the market, the ω-conotoxin, ziconotide. This peptide potently and selectively inhibits Cav2.2, resulting in analgesia in chronic pain states. However, this drug is only available via intrathecal administration, and adverse effects and a narrow therapeutic window have limited its use in the clinic. Other Cav2.2 inhibitors are currently in development and offer the promise of an improved route of administration and safety profile. This review assesses the potential of targeting VGCCs for analgesic development, with a main focus on conotoxins that block Cav2.2 and the developments made to transform them into therapeutics.
Keyword Voltage-gated calcium channel
Omega-conotoxin
Structure activity relationships
Cav2
Q-Index Code CX
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Non HERDC
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