Overview
Ziconotide (brand name: Prialt) is a synthetic 25-amino acid peptide derived from the omega-conotoxin MVIIA found in the venom of the predatory marine cone snail Conus magus. It is the first and only N-type calcium channel blocker approved for clinical pain management, receiving FDA approval in December 2004. Delivered by continuous intrathecal infusion via an implanted pump, Ziconotide provides potent analgesia in patients with severe chronic pain refractory to systemic analgesics and intrathecal morphine. It is non-opioid and carries no addiction liability.
Mechanism of action
Ziconotide selectively and reversibly binds to N-type voltage-sensitive calcium channels (Cav2.2) located on the presynaptic terminals of primary afferent nociceptive neurons in the dorsal horn of the spinal cord. By blocking calcium influx through these channels, Ziconotide inhibits the depolarization-evoked exocytotic release of pro-nociceptive neurotransmitters including glutamate, substance P, and calcitonin gene-related peptide (CGRP). This interrupts ascending pain signal transmission without affecting opioid receptors, rendering it effective in opioid-tolerant patients. Its 25-amino-acid structure contains three disulfide bridges forming a rigid, loop-constrained backbone that confers high channel selectivity. Cerebrospinal fluid (CSF) delivery is required because the peptide's size prevents oral or systemic bioavailability.
Dosing protocols
| Purpose | Route | Dosage | Frequency | Notes |
|---|---|---|---|---|
| severe chronic pain management (FDA-approved intrathecal) | intravenous | 0.5–19.2 mcg/day | continuous intrathecal infusion | Start at no more than 2.4 mcg/day; titrate by ≤2.4 mcg/day every 24 hours. Maximum approved dose: 19.2 mcg/day. Dose adjustments require specialist supervision. Slow titration minimizes psychiatric and neurological adverse events. |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
Multiple randomized controlled trials (RCTs) established clinical efficacy. A pivotal double-blind RCT (Staats et al., 2004, JAMA) demonstrated a 31.2% reduction in visual analog scale (VAS) pain scores versus 6.0% for placebo in patients with refractory malignant or non-malignant pain. Additional trials confirmed efficacy in cancer pain, AIDS-related pain, and neuropathic pain. Long-term extension studies spanning up to 3 years show sustained analgesia without tolerance development. Narrow therapeutic index and significant CNS side effect burden at higher doses require careful dose titration under specialist supervision.
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Legal status
FDA-approved (NDA 021060, December 28, 2004) for management of severe chronic pain via intrathecal infusion. Prescription-only; requires implanted intrathecal drug delivery system. Available as Prialt 25 mcg/mL intrathecal solution. REMS program is not required but off-label use outside intrathecal route is not established.
Where to get it
Prescription required
Ziconotide is a prescription medication. Consult your healthcare provider or a licensed telehealth platform for access.