Ziconotide

Prialt, SNX-111, synthetic ω-conotoxin MVIIA, CI-1009

Cognitive & neuro

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. Ziconotide is an approved prescription medicine delivered only by an implanted or external pump into the fluid around the spinal cord. It is one of the most toxic peptides on this site if misused, has a boxed warning for psychiatric and neurological harm, and has no self-directed or community use. This page explains the published science.

Summary

Class: Synthetic copy of ω-conotoxin MVIIA, a 25-amino-acid peptide with three disulfide bonds from the venom of the cone snail Conus magus
Mechanism: Blocks N-type (CaV2.2) voltage-gated calcium channels on pain-nerve terminals in the spinal cord, stopping release of pain neurotransmitters
Routes studied: Intrathecal (into the cerebrospinal fluid) only; intravenous was tested early and abandoned because of blood-pressure effects
Half-life: ~4.6 h in cerebrospinal fluid (range ~2.9–6.5 h); negligible plasma levels
Storage: Vials (25 µg/mL and 100 µg/mL) refrigerated 2–8 °C, protected from light; do not freeze. Diluted solution in pump stable for weeks per label (refill intervals set accordingly)
Regulatory status: Approved medicine (US 2004, EU 2005, UK); specialist pain-clinic use only

Doses are as reported in studies or by the community — never recommendations.

1What it is

Ziconotide is the exact synthetic version of a toxin that the fish-hunting cone snail Conus magus uses to paralyse prey. Cone snail venoms contain hundreds of small, tightly folded peptides ("conotoxins"), each targeting a specific ion channel; MVIIA was identified by Baldomero Olivera's group at the University of Utah in the 1980s as a highly selective blocker of the N-type calcium channel. Because that channel sits on the terminals of pain-sensing nerves where they enter the spinal cord, researchers reasoned that delivering the toxin directly into spinal fluid could switch off pain transmission without opioids. Neurex, then Elan, developed it; the FDA approved it in December 2004 and the EU in February 2005 for severe chronic pain in people who need intrathecal therapy and cannot tolerate or have failed other treatments, including intrathecal morphine.

It is the only approved conotoxin and the only non-opioid approved for intrathecal pain. It does not cause tolerance, dependence or respiratory depression, but it has a narrow margin between effect and serious psychiatric and neurological side effects, so dosing is slow and the drug is restricted to specialist pain services.

2How it's thought to work

Pain signals from the body arrive at the dorsal horn of the spinal cord and are passed on by releasing glutamate, substance P and CGRP. That release depends on calcium entering the nerve terminal through N-type channels. Ziconotide plugs those channels.

Unlike opioids it does not act on receptors that adapt with repeated use, so there is no tolerance; it also does nothing for the breathing centres, so overdose does not stop breathing.

The same channels exist throughout the brain, which is why drug that spreads up the spinal fluid causes dizziness, confusion, hallucinations and memory problems. The slow-titration protocol exists to find the lowest effective dose before those appear.

It does not cross from blood to brain and is broken down by peptidases in blood, so systemic doses do nothing for pain and cause hypotension — hence intrathecal only.

A synthetic copy of a cone snail toxin that plugs the N-type calcium channel on pain-carrying nerve endings in the spinal cord. No calcium in, no transmitter released, no pain signal passed on — and no tolerance, because it is not an opioid receptor.Schematic — not to scale

3What the research shows

Severe chronic pain in cancer and AIDS

A randomised, placebo-controlled trial (n=111) using fast titration found a 53% improvement in pain scores versus 18% with placebo, but with a high rate of serious adverse events (Staats 2004, JAMA). [2]

Severe chronic non-malignant pain

A second placebo-controlled trial (n=255) using fast titration showed a smaller but significant benefit (31% vs 6% improvement) and again many neurological side effects (Wallace 2006, Neuromodulation). A third trial (n=220) using the slow titration now on the label (starting 0.1 µg/h, increasing over 3 weeks) found a modest effect — pain score fell 14.7% vs 7.2% with placebo — with far better tolerability (Rauck 2006, J Pain Symptom Manage). The approved dosing is based on this third trial. [3][4]

Long-term open-label use

Open-label extension data on over 600 patients showed maintained analgesia in responders over months to years without tolerance; roughly a third to a half discontinued for side effects or lack of effect (Webster 2009, J Pain Symptom Manage; Ellis 2008, Pain Pract). [5]

Combination with intrathecal morphine or other agents

Small open-label studies suggest additive benefit when added to intrathecal opioids or baclofen (Wallace 2008, Pain Med; Alicino 2012, Pain). No large .

Community / self-directed use

None documented; impossible without an intrathecal catheter, and potentially fatal if attempted by any other route.

4Reported side effects and interactions

Literature-reported

Boxed warning: severe psychiatric symptoms and neurological impairment — confusion, hallucinations, paranoia, depression, suicidal thinking, unresponsiveness and stupor — which may appear late in treatment and usually resolve over days to weeks after stopping (it has a long from CSF). Contraindicated in people with a history of psychosis. Common (>10%): dizziness, nausea, confusion, nystagmus (jerky eye movement), memory impairment, unsteady gait, sleepiness, headache, blurred vision, weakness, urinary retention. Raised serum creatine kinase in up to 40%, occasionally with muscle pain; rare rhabdomyolysis. Meningitis from the pump system (about 3% in trials, mostly with external catheters). Because reversal requires stopping the infusion and waiting, slow titration is the main safety tool.

Community-reported

none; no community use.

Theoretical. N-type channel blockade in the heart or vessels if drug reached the circulation at high dose causes hypotension (seen in early IV studies).

Interactions. additive sedation and confusion with opioids, benzodiazepines, antidepressants and other CNS depressants (pharmacodynamic). Must not be given with intrathecal chemotherapy (EU label). No CYP interactions; it is cleared by peptidases in CSF.

Markers researchers commonly monitor

These follow the label and pain-service protocols:

Marker	Why it's watched
Serum creatine kinase (CK)	the one specific blood marker; checked at baseline, every other week for the first month, then monthly; a rise with muscle pain or weakness prompts dose reduction or stopping.
Mental status, mood and cognition (structured questions at each visit)	psychiatric and cognitive harm is the boxed-warning risk and can be gradual.
Gait and balance	ataxia and falls are common; assessed clinically.
Temperature, headache and neck stiffness	signs of meningitis from the catheter or pump.
Pain scores (e.g. VASPI) and function	the efficacy measure; the trials used a 100-mm visual analogue scale.
Urine output / bladder symptoms	urinary retention is reported.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Pain-clinic use only. The 25 µg/mL vial is used undiluted for low starting rates; the 100 µg/mL vial is diluted with preservative-free 0.9% saline to the concentration needed for the pump. Vials are single-use; the pump reservoir is refilled under sterile conditions, and refill intervals are shorter when the drug is diluted because the diluted peptide degrades faster at body temperature. The site calculator is not applicable.

6Commonly studied alongside

Intrathecal morphine and hydromorphone, intrathecal baclofen (spasticity), intrathecal bupivacaine and clonidine in polyanalgesic regimens. No research-community pairings exist. For context, other venom-derived peptides on the site include eptifibatide (profile 132, snake venom) and exenatide (lizard saliva, earlier profile).

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	FDA-approved (Prialt, December 2004) for severe chronic pain requiring intrathecal therapy; TerSera Therapeutics is the current holder
European Union	EMA-authorised (Prialt, 21 February 2005); MAH Esteve Pharmaceuticals GmbH; orphan status removed 2015; product information last updated April 2026
United Kingdom	MHRA-licensed; distributed under Esteve / Riemser †
Australia	TGA-registered (Prialt) †
South Africa	Not registered with SAHPRA †
Sport	Not prohibited by WADA

8Open questions

Why response varies so widely between patients; no predictive marker exists.
Whether newer N-type channel blockers (oral or intrathecal) can keep the analgesia and lose the CNS effects.
Optimal position in intrathecal algorithms versus morphine as first line — some guidelines (PACC) list it as first-line intrathecal monotherapy, but comparative are lacking.

9References

1Olivera BM et al. (1987). Neuronal calcium channel antagonists: discrimination between calcium channel subtypes using ω-conotoxin from Conus magus venom. Biochemistry. PubMed · DOI
2Staats PS et al. (2004). Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial. JAMA. PubMed · DOI
3Wallace MS et al. (2006). Intrathecal ziconotide in the treatment of chronic nonmalignant pain: a randomized, double-blind, placebo-controlled clinical trial. Neuromodulation. PubMed · DOI
4Rauck RL et al. (2006). A randomized, double-blind, placebo-controlled study of intrathecal ziconotide in adults with severe chronic pain. J Pain Symptom Manage. PubMed · DOI
5Webster LR et al. (2009). Open-label, multicenter study of combined intrathecal morphine and ziconotide: addition of ziconotide in patients receiving intrathecal morphine for severe chronic pain. Pain Med. [verify exact title/journal] PubMed
6Deer TR et al. (2017). The Polyanalgesic Consensus Conference (PACC): recommendations on intrathecal drug infusion systems best practices and guidelines. Neuromodulation. PubMed · DOI
7Prialt (ziconotide intrathecal infusion) US prescribing information and EU Summary of Product Characteristics (current). PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

30 Oct 2026Profile published — awaiting medical review

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