Ziconotide is a 25-amino-acid peptide (MW ~2639 g/mol) derived from the omega-conotoxin MVIIA found in the venom of the marine cone snail Conus magus. It selectively blocks N-type voltage-gated calcium channels (Cav2.2) in the spinal cord dorsal horn. Ziconotide was FDA-approved in December 2004 (Prialt) for the management of severe chronic pain in patients who are intolerant of or refractory to other treatments and is administered exclusively via intrathecal infusion through an implanted pump system.
Category: Pain / Calcium Channel Blocker. Evidence rating: A (strong human clinical data).
Clinical status: FDA-approved (Prialt for severe chronic pain via intrathecal infusion, December 2004)
Ziconotide is a potent and selective blocker of N-type voltage-gated calcium channels (Cav2.2) located on presynaptic terminals of primary afferent nociceptors in the dorsal horn of the spinal cord. By blocking calcium entry through Cav2.2 channels, ziconotide prevents the release of…
Safety considerations: Common (>=10%): dizziness (47%), nausea (30%), confusion (33%), headache (15%), somnolence, nystagmus, abnormal gait, memory impairment; Serious neuropsychiatric effects: cognitive impairment, hallucinations, psychosis, changes in consciousness, new or worsening depression, suicidal ideation; serum CK elevation and rhabdomyolysis reported rarely; Must be administered via intrathecal pump only; dose must be titrated slowly (no more than 2.4 mcg/day initially, increases no more than 2.4 mcg/day at intervals no shorter than 2-3 times per week) to minimize CNS adverse effects.
Reviewed by the PeptideAtlas Editorial Team.
| Amino-acid sequence | CKGKGAKCSRLMYDCCTGSCRSGKC (3 disulfide bonds: C1-C16, C8-C20, C15-C25) |
|---|---|
| Molecular weight | ~2639 g/mol |
| CAS number | 107452-89-1 |
| Half-life | ~4.6 hours (CSF) |
| Production method | synthetic |
| Anti-doping status | not-listed |
| US regulatory status | FDA-approved (Prialt, December 2004) for severe chronic pain via intrathecal infusion in patients intolerant of or refractory to other therapies. |
Ziconotide does not cross the blood-brain barrier and would be rapidly degraded if given systemically. It must be delivered directly into the cerebrospinal fluid via an implanted intrathecal pump to reach its target (Cav2.2 calcium channels on spinal cord dorsal horn neurons).
No. Ziconotide is a non-opioid analgesic that works by blocking N-type calcium channels. It has no activity at opioid receptors, no risk of respiratory depression, no physical dependence, and no cross-tolerance with opioids. It can be used in patients who have failed opioid therapy.
Ziconotide is a synthetic version of omega-conotoxin MVIIA, a peptide found in the venom of Conus magus, a predatory marine cone snail. The snail uses this toxin to paralyze prey by blocking nerve signal transmission. The pharmaceutical form is produced by chemical peptide synthesis.
Coverage on this site: Macrocyclic Peptide Drugs: Structures, Pipelines and Oral Prospects.