Overview
Ziconotide (Prialt) is a 25-amino acid synthetic equivalent of ω-conotoxin MVIIA, a peptide toxin from the cone snail Conus magus. FDA-approved in 2004 for severe chronic pain, it represents a first-in-class N-type calcium channel blocker. Because it cannot cross the blood-brain barrier, ziconotide is administered by intrathecal infusion directly into the cerebrospinal fluid. It is indicated for patients with refractory pain who have failed or cannot tolerate systemic opioids or other analgesics.
Mechanism of Action
Ziconotide selectively blocks N-type voltage-gated calcium channels (Cav2.2) in the spinal cord's dorsal horn laminae I and II. N-type channels are the primary calcium entry route mediating neurotransmitter release from primary afferent C-fibers and Aδ-fibers. Blocking these channels prevents calcium influx, inhibiting substance P, glutamate, and CGRP release from nociceptive afferents and interrupting pain signal transmission without activating opioid receptors. This mechanism means there is no cross-tolerance with opioids and no respiratory depression risk.
Potential Benefits
- Potent analgesia for severe chronic and refractory pain
- Non-opioid mechanism with no addiction potential
- No respiratory depression
- Effective for neuropathic, cancer, and AIDS-related pain
- No tolerance development in long-term use
Research Dosage Notes
The following reflects doses used in published research studies. This is not medical advice.
Intrathecal infusion only: starting dose 2.4 mcg/day, titrated to max 19.2 mcg/day. Not for IV or epidural use.
Amino Acid Sequence
Cys-Lys-Gly-Lys-Gly-Ala-Lys-Cys-Ser-Arg-Leu-Met-Tyr-Asp-Cys-Cys-Thr-Gly-Ser-Cys-Arg-Ser-Gly-Lys-Cys-NH2 (three disulfide bonds)
Side Effects & Safety
- Dizziness, nausea, confusion (dose-limiting CNS effects)
- Psychiatric symptoms at higher doses (hallucinations, agitation)
- Catheter/pump complications (device-related)
- Severe psychiatric events require immediate discontinuation
Synergistic Compounds
The following compounds have been studied alongside Ziconotide for potential complementary or synergistic effects:
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References & Further Reading
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