Summary

Ziconotide is a synthetic 25-amino-acid peptide derived from cone snail (Conus magus) venom, acting as a selective N-type voltage-gated calcium channel (Cav2.2) blocker. Approved by the FDA (2004) and EMA (2005) as Prialt for severe chronic pain, ziconotide is administered intrathecally and is reserved for patients refractory to or intolerant of other analgesics. It is the first conopeptide approved for human therapeutic use. This profile is for research and educational purposes only.

Mechanism

Ziconotide selectively blocks N-type voltage-gated calcium channels (Cav2.2) in the spinal cord. Cav2.2 channels are located on presynaptic terminals of primary afferent nociceptive neurons in the dorsal horn. By blocking these channels, ziconotide inhibits calcium influx, preventing the release of excitatory neurotransmitters (substance P, glutamate, calcitonin gene-related peptide) from primary afferent fibres. This reduces nociceptive transmission at the spinal level. Ziconotide does not bind opioid receptors and has no opioid-like dependence or respiratory depression liability.

Evidence base

Ziconotide has strong evidence from three pivotal phase 3 placebo-controlled trials demonstrating analgesic efficacy in both cancer and non-cancer pain. Long-term open-label data (n=784) support sustained efficacy. The evidence base is robust but the clinical utility is constrained by the narrow therapeutic window, neuropsychiatric adverse effects, and the requirement for intrathecal delivery. Real-world use is limited to refractory cases managed by specialist pain centres.

Protocols

Ziconotide is a licensed prescription medicine requiring specialist intrathecal administration. In clinical practice, it is initiated at 2.4 mcg/day intrathecally and titrated in 2.4 mcg/day increments every 2-3 days to a typical maintenance of 6.9-25.8 mcg/day via implanted pump. These protocols are described for research reference only and do not constitute dosing advice.

Ziconotide is classified as a Prescription-Only Medicine (POM) in the United Kingdom. Prialt is licensed by the MHRA for severe chronic pain refractory to other treatments. It is available exclusively through specialist NHS pain centres with intrathecal drug delivery expertise. Supply without a prescription is unlawful. Unregulated purchase is extremely hazardous due to the requirement for sterile intrathecal administration.

Vendor notes

Ziconotide is a licensed POM available only through specialist NHS pain centres with intrathecal delivery expertise. We do not list research-grade vendors for this compound. Researchers requiring ziconotide for in vitro or animal studies should source from established biochemical supply companies (e.g., Sigma-Aldrich, Tocris, Alomone Labs) with appropriate COAs.

References

  1. Staats PS, Yearwood T, Charapata SG, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial. JAMA. 2004;291(1):63-70.
  2. Wallace MS, Rauck R, Fisher R, et al. Intrathecal ziconotide for severe chronic pain: safety and tolerability during long-term continuous exposure. Pain Med. 2006;7(1):39-48.
  3. Penn RD, Paice JA. Adverse effects associated with the intrathecal administration of ziconotide. Pain. 2000;85(1-2):291-296.
  4. Rauck RL, Wallace MS, Leong MS, et al. A randomized, double-blind, placebo-controlled study of intrathecal ziconotide in adults with severe chronic pain. J Pain Symptom Manage. 2006;31(5):393-406.
  5. Miljanich GP. Ziconotide: neuronal calcium channel blocker for treating severe chronic pain. Curr Med Chem. 2004;11(23):3029-3040.