{"id":"ziconotide","name":"Ziconotide","aliases":["Prialt","SNX-111","ω-conotoxin MVIIA"],"url":"https://lyoresearch.com/compounds/ziconotide","class":{"id":"endocrine-medicines","name":"Established peptide medicines","url":"https://lyoresearch.com/classes/endocrine-medicines"},"summary":"Ziconotide is a synthetic copy of a 25-amino-acid peptide from the venom of the cone snail Conus magus, approved as Prialt in 2004 for severe chronic pain in people who need intrathecal therapy. It blocks N-type calcium channels in the spinal cord — a mechanism unrelated to opioids, with no tolerance and no dependence. In its cancer and AIDS pain trial, pain scores improved 53.1% against 18.1% on placebo. It carries a boxed warning for severe psychiatric and neurological effects.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"3 phase 3 RCTs; the one quoted here randomised 111 patients","regulatory_status":"Approved (Rx)","molecule":{"formula":"C102H172N36O32S7","molecular_weight":"2639.2","cas":"107452-89-1","pubchem_cid":16135415,"sequence":"CKGKGAKCSRLMYDCCTGSCRSGKC-NH2","sequence_note":"Three disulfide bridges.","note":null},"pharmacokinetics":{"basis":"label","route":"Intrathecal infusion by implanted or external pump","half_life":"About 4.6 hours terminal half-life in cerebrospinal fluid","licensed_regimen":"A continuous intrathecal infusion started at a low rate and titrated slowly upward within the label's maximum, with psychiatric and neurological monitoring","product":"Prialt","source":{"title":"Prialt prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b025d8ed-937d-4597-9ad1-0b2f6e0ee5b1"}},"outcomes":[{"outcome":"Severe cancer or AIDS-related pain","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"1 phase 3 RCT (n=111)","evidence":"A randomised placebo-controlled trial in 111 patients with severe pain despite intrathecal opioids found a mean 53.1% improvement in pain scores against 18.1% on placebo, sustained through the maintenance phase. The result is real and the record is messy: JAMA later published a notice of duplicate publication about this article and an accompanying editorial.","references":[{"citation":"Staats PS, Yearwood T, Charapata SG, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial.","where":"JAMA, 2004;291:63–70","url":"https://pubmed.ncbi.nlm.nih.gov/14709577/"},{"citation":"Notice of duplicate publication.","where":"JAMA, 2004","url":"https://pubmed.ncbi.nlm.nih.gov/15479927/"},{"citation":"Duplicate publication, multiple problems (editorial).","where":"JAMA, 2004","url":"https://pubmed.ncbi.nlm.nih.gov/15479941/"}],"verbatim":{"text":"Mean VASPI scores improved 53.1% (95% confidence interval [CI], 44.0%-62.2%) in the ziconotide group and 18.1% (95% CI, 4.8%-31.4%) in the placebo group (P<.001), with no loss of efficacy of ziconotide in the maintenance phase.","citation":"Staats PS, Yearwood T, Charapata SG, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial.","url":"https://pubmed.ncbi.nlm.nih.gov/14709577/"}},{"outcome":"Absence of tolerance and dependence","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"Phase 3 programme; label","evidence":"Ziconotide does not act on opioid receptors, so there is no tolerance, no dose escalation of the kind opioids require, and no withdrawal syndrome. The trial's maintenance phase showed no loss of effect. This is the central clinical argument for a drug that is otherwise very hard to use.","references":[{"citation":"Staats PS, Yearwood T, Charapata SG, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial.","where":"JAMA, 2004;291:63–70","url":"https://pubmed.ncbi.nlm.nih.gov/14709577/"},{"citation":"Prialt (ziconotide) intrathecal infusion prescribing information.","where":"DailyMed, read 29 Oct 2026","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b025d8ed-937d-4597-9ad1-0b2f6e0ee5b1"}]},{"outcome":"Severe psychiatric and neurological effects","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":true,"human_studies":"Label boxed warning; approval programme","evidence":"The Prialt label's boxed warning states that severe psychiatric symptoms and neurological impairment may occur during treatment, and that the drug is contraindicated in patients with a pre-existing history of psychosis. Hallucinations, confusion, depression and in some cases suicidality have been reported, and monitoring for cognitive and psychiatric change is built into the label. The dose–harm relationship is the limiting factor in practice.","references":[{"citation":"Prialt (ziconotide) intrathecal infusion prescribing information.","where":"DailyMed, read 29 Oct 2026","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b025d8ed-937d-4597-9ad1-0b2f6e0ee5b1"}]},{"outcome":"Delivery burden","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":true,"human_studies":"Label","evidence":"Ziconotide is given only by continuous intrathecal infusion through an implanted or external pump — a surgical commitment with the infection and device risks that accompany it, and the reason it is a last-line therapy rather than an alternative to oral analgesia.","references":[{"citation":"Prialt (ziconotide) intrathecal infusion prescribing information.","where":"DailyMed, read 29 Oct 2026","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b025d8ed-937d-4597-9ad1-0b2f6e0ee5b1"}]}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Prialt authorised centrally in 2005 for severe chronic pain in patients requiring intrathecal analgesia. Specialist hospital use."},{"region":"United States","status":"Approved, prescription-only","note":"Prialt approved in 2004 for severe chronic pain in patients for whom intrathecal therapy is warranted and who are intolerant of or refractory to other treatment. Boxed warning; contraindicated with a pre-existing history of psychosis."},{"region":"United Kingdom","status":"Licensed, prescription-only","note":"Prialt licensed by the MHRA for intrathecal use."},{"region":"Australia","status":"Registered, Schedule 4","note":"Registered for intrathecal use."},{"region":"Canada","status":"Not marketed","note":"No current Drug Identification Number for ziconotide."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Not named on the Prohibited List."}],"faq":[{"q":"Is ziconotide stronger than morphine?","a":"It is not comparable — it works on a different target, and it is used when intrathecal opioids have failed. In its trial in severe cancer and AIDS pain, scores improved 53% against 18% on placebo in patients already receiving intrathecal opioids."},{"q":"Why the psychiatric boxed warning?","a":"The calcium channels it blocks in the spinal cord also exist throughout the brain. Hallucinations, confusion and depression can occur, the label contraindicates it in anyone with a history of psychosis, and psychiatric monitoring is part of its use."},{"q":"Can ziconotide be injected or taken orally?","a":"No. It does not cross the blood-brain barrier, so it has to be infused directly into cerebrospinal fluid through a pump. There is no systemic formulation and no self-administered route."}],"references":[{"cite":"Staats PS, Yearwood T, Charapata SG, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial.","where":"JAMA, 2004;291:63–70","url":"https://pubmed.ncbi.nlm.nih.gov/14709577/","note":"111 randomised. See the duplicate-publication notice below before citing this trial's size or novelty."},{"cite":"Notice of duplicate publication.","where":"JAMA, 2004","url":"https://pubmed.ncbi.nlm.nih.gov/15479927/","note":"The journal's notice concerning the ziconotide trial above."},{"cite":"Duplicate publication, multiple problems (editorial).","where":"JAMA, 2004","url":"https://pubmed.ncbi.nlm.nih.gov/15479941/","note":"Editorial accompanying the notice."},{"cite":"Prialt (ziconotide) intrathecal infusion prescribing information.","where":"DailyMed, read 29 Oct 2026","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b025d8ed-937d-4597-9ad1-0b2f6e0ee5b1","note":"Boxed warning, contraindication in pre-existing psychosis, intrathecal route, CSF terminal half-life about 4.6 hours, and the 25-amino-acid structure with three disulfide bonds."},{"cite":"PubChem compound record: ziconotide.","where":"PubChem, read 29 Oct 2026","url":"https://pubchem.ncbi.nlm.nih.gov/compound/16135415","note":"Formula, molecular weight, CAS and the 25-residue sequence used on this page."}],"last_reviewed":"2026-10-29","literature_searched_to":"2026-10-29","changelog":[{"date":"2026-10-29","note":"Initial publication. Grade B on the pivotal trial, held below A because of the duplicate-publication notice; the psychiatric boxed-warning row graded A."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}