Ziconotide

A synthetic 25-residue omega-conotoxin MVIIA from the cone snail Conus magus that blocks N-type voltage-gated calcium channels; FDA-approved as Prialt (2004) for severe chronic pain by intrathecal infusion only.

Also referenced as: Prialt, omega-conotoxin MVIIA, ziconotide acetate, SNX-111

Also appears in: Neuroprotection

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What is Ziconotide?

Ziconotide is the synthetic form of omega-conotoxin MVIIA, a 25-amino-acid peptide with three disulfide bonds originally isolated from the venom of the fish-hunting marine cone snail Conus magus. It is a selective blocker of N-type (Cav2.2) voltage-gated calcium channels and was approved by the FDA on December 28, 2004 as Prialt for the management of severe chronic pain in adults who need intrathecal therapy and are intolerant of or refractory to other treatments. Unlike most peptides covered on this site, ziconotide has essentially no research-market or self-administration footprint: it is delivered only into the cerebrospinal fluid through an implanted or external microinfusion pump, so it appears here as a reference point for a clinically approved peptide analgesic rather than as a compound sold to researchers.

How it works

• Selective N-type calcium channel blockade — ziconotide binds the pore-forming subunit of Cav2.2 channels with high affinity and effectively no activity at L-type or other channel subtypes; the toxin was first purified from Conus magus venom, chemically synthesized, and shown to discriminate between neuronal calcium channel subtypes by Olivera and colleagues (Olivera et al., Biochemistry, 1987)
• Presynaptic inhibition in the dorsal horn — N-type channels are concentrated on the central terminals of primary nociceptive afferents in laminae I and II of the spinal cord; blocking them reduces calcium influx and the release of glutamate, substance P, and CGRP that transmit pain signals to second-order neurons (Miljanich, Current Medicinal Chemistry, 2004)
• Non-opioid pharmacology — ziconotide does not act at opioid receptors, is not a controlled substance, and did not produce tolerance in animal models or long-term clinical use, which is why it is positioned as an alternative to intrathecal morphine rather than an adjunct to it (Schmidtko et al., The Lancet, 2010, review)
• Neuroprotective activity in ischemia models — the compound (then designated SNX-111) protected CA1 hippocampal neurons after transient global cerebral ischemia in rats, even when a single intravenous bolus was given up to 24 hours after the insult; notably, the same study found that neuroprotection did not track a conopeptide’s ability to block glutamate release, so the mechanism is not simply reduced excitotoxicity; the stroke indication was taken into early trials but never developed to approval (Valentino et al., Proceedings of the National Academy of Sciences, 1993)

Research status

Ziconotide is an approved drug with a mature, if narrow, evidence base built on three pivotal placebo-controlled trials and two decades of intrathecal pain-practice guidance.

• Staats et al. (2004), JAMA 291(1):63–70 — 111 adults with refractory cancer or AIDS pain randomized 2:1 to intrathecal ziconotide or placebo, titrated over 5 to 6 days; mean pain scores improved 53.1% versus 18.1% (P < 0.001), with moderate-to-complete relief in 52.9% versus 17.5%. Fast titration to high doses produced frequent central nervous system adverse events, and across the trial program the label reports meningitis in 3% of ziconotide-treated patients, concentrated in those with external microinfusion devices and catheters.
• Wallace et al. (2006), Neuromodulation 9(2):75–86 — the chronic nonmalignant pain trial (Study 96-002) randomized 255 patients (169 ziconotide, 86 placebo) to a 6-day inpatient titration starting at 0.4 mcg/hour; mean pain reduction was 31.2% versus 6.0% (P ≤ 0.001), but the ziconotide arm reported significantly more adverse events (abnormal gait, dizziness, nystagmus, nausea, urinary retention), and the starting and maximum doses had to be cut mid-trial because of them.
• Rauck et al. (2006), J Pain Symptom Manage 31(5):393–406 — Study 301 randomized 220 patients with severe chronic pain to slow titration starting at 0.1 mcg/hour (2.4 mcg/day) over three weeks. The effect size shrank (14.7% versus 7.2% improvement, P = 0.036), but tolerability improved markedly; this slow, low-dose titration became the labeled approach.
• Guidance — the 2017 Polyanalgesic Consensus Conference (Deer et al., Neuromodulation 20(2):96–132) recommends ziconotide alongside morphine as a first-line intrathecal monotherapy for both cancer and non-cancer pain, with trial titration and pre-implant psychological screening emphasized.
• Post-approval work — small investigator-initiated studies have examined bolus trialing and conservative first-line dosing (for example NCT03321955, Albany Medical College, phase 4, 13 patients, completed December 2020 with no posted results); a phase 4 single-shot study in painful neuropathy or myelopathy (NCT01992562) was withdrawn for logistical and recruitment problems. The current sponsor, ESTEVE, is running an observational study of intrathecal ziconotide in non-cancer pain (NCT06541184, recruiting, about 85 patients planned, started October 2024, estimated completion October 2029).
• Commercial status — ESTEVE, which already sold Prialt in Europe, announced its acquisition of TerSera Therapeutics’ infusion specialty therapies unit (Prialt and Quzyttir) in January 2026 and closed it on March 10, 2026; the US label was revised in August 2026 under Esteve Pharmaceuticals. Drugs@FDA lists the three current vial presentations as prescription products (only the old 200 mcg/2 mL vial is discontinued), and no withdrawal or discontinuation has been announced as of November 2026.

Common dosage forms

Prialt is supplied only as a sterile, preservative-free solution for intrathecal infusion in single-use glass vials: 25 mcg/mL in a 20 mL vial, and 100 mcg/mL in 1 mL and 5 mL vials. Administration requires a programmable implanted microinfusion pump (the current label names the Medtronic SynchroMed II and SynchroMed III systems; the 2023 label also named the CADD-Micro external ambulatory pump) or an external microinfusion device driving a temporary intrathecal catheter. There is no oral, subcutaneous, intravenous, or nasal formulation, and ziconotide is not a compound that circulates as a lyophilized research vial in the way most research peptides do.

Key considerations

• Approved, but strictly specialist-administered — the FDA Approved status reflects Prialt’s December 2004 approval for severe chronic pain by intrathecal infusion; ziconotide has no compounding, self-administration, or research-market pathway and is used only by pain and neurosurgical teams with intrathecal pump programs, and its neuroprotection evidence is strictly preclinical.
• Boxed warning for neuropsychiatric adverse reactions — the label warns of severe psychiatric symptoms and neurological impairment, including hallucinations (12% of trial patients), paranoid reactions (3%), delirium, confusion, decreased consciousness, and unresponsiveness; ziconotide is contraindicated in anyone with a pre-existing history of psychosis, and patients are monitored frequently with interruption or discontinuation on serious signs.
• Narrow therapeutic window — efficacy and central nervous system toxicity sit close together, which is why the pivotal fast-titration trials showed large effects with poor tolerability while the slow-titration trial showed better tolerability with a modest effect; the drug is appropriate for a small subset of severe chronic pain patients.
• Other labeled safety signals — elevated serum creatine kinase (sometimes with myopathy), meningitis and other infections associated with the microinfusion device (highest risk with external systems), and the need to taper rather than abruptly stop concomitant opioids; ziconotide itself has no abuse or dependence liability and is not scheduled.
• Naming — “ziconotide,” “omega-conotoxin MVIIA,” and the development code “SNX-111” refer to the same molecule; it should not be confused with other conotoxins (such as omega-conotoxin GVIA from Conus geographus) or with the alpha-conotoxins studied for nicotinic receptor targets, none of which are approved drugs.