Targeting voltage-gated calcium channels for the treatment of neuropathic pain: a review of drug development

Abstract

Introduction: Pain is a major burden for affected individuals and society, and controlling neuropathic pain is especially challenging. The number of drugs available is limited and treatments are often marginally effective and burdened by side effects. Voltage-gated calcium channels (VGCC) play a major role in the development and maintenance of neuropathic pain and are thus prime targets for its treatment.

Areas covered: Currently available drugs that target the calcium channel include ziconotide, gabapentin and pregabalin. While there are no VGCC blockers currently in clinical trials, there are many in development. Recently, orally available, use-dependent compounds have been reported. We will review, in detail, compounds currently in development and include a brief review of VGCC and the drugs currently in use.

Expert opinion: There is real hope that new drugs targeting calcium channels will soon be available. This hope is based on advancing technologies for peptide synthesis, more efficient drug screening and orally available, use-dependent compounds. Some form of direct VGCC blockade or modulation will always have a place in the treatment of neuropathic pain, but given the complexity and neuroplasticity of pain transmission, polypharmacy will likely be required for many chronic pain sufferers for the foreseeable future.

Keywords:

• conotoxin
• neuropathic pain
• N-type channel
• T-type channel
• Voltage-gated calcium channel

Acknowledgements

Special thanks to S Sritongsook and the Scripps Mercy Library for assisting with the collection of references.

Notes

This box summarizes key points contained in the article.