Leconotide
A cone snail peptide developed as a pain drug that could be injected ordinarily, and then dropped
Leconotide (omega-conotoxin CVID, AM336, CNSB004) is a 27-residue peptide copied from the venom of the cone snail Conus catus. It blocks N-type calcium channels, the same target as the approved pain drug ziconotide, but it was pursued because animal work suggested it could relieve pain given into a vein rather than through a spinal catheter. One early intrathecal study in cancer patients was never published, no trial is registered, and development stopped. Everything on this page below the history is animal or laboratory work.
No established human dose Details ↓
Recommended Dosing
No established human dose
No published study has given leconotide to a person, so this page states no dose. Every amount on it comes from rats, mice, rabbits or monkeys, given into the spinal fluid, a vein or under the skin, and an animal amount cannot be converted into a human one.
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What is it?
Leconotide is a 27-amino-acid peptide that blocks N-type calcium channels, the gates that let calcium into nerve endings and so allow them to release their transmitters. Its sequence was copied from a peptide in the venom of Conus catus, a cone snail that hunts fish; the snail's own use for it is to stop its prey's nerves working. Pharmacologists who went looking for N-type blockers in cone snail venom in the 1990s found four in this species and labelled them CVIA to CVID. CVID became the drug candidate, and over twenty-five years it has been called several things: omega-conotoxin CVID in the pharmacology papers, AM336 while Amrad developed it, CNSB004 and then leconotide afterwards. FDA's substance registry files all of that under one entry, UNII 2P1P5JB93S, with the sequence CKSKGAKCSKLMYDCCSGSCSGTVGRC, an amide at the end and three disulfide bonds holding the molecule in shape.
The reason anyone built a drug out of this is that one N-type channel blocker already works. Ziconotide, the synthetic version of a peptide from a different cone snail, has been approved in the United States since 2004 for severe chronic pain, and it is a real option for people whose pain does not answer to opioids. But it has to be pumped into the spinal fluid through an implanted catheter, because given any other way it causes dizziness, confusion and blood-pressure problems before it relieves pain. Leconotide was taken up as the peptide that might not have that limitation: in binding assays it told N-type channels apart from the closely related P/Q-type ones more sharply than any earlier omega-conotoxin, and it let go of the channel quickly rather than hanging on.
In animals those properties did show up. Spinal doses relieved nerve-injury and inflammatory pain in rats at amounts about ten times below the ones that made the animals clumsy, a wider margin than MVIIA managed in the same experiments. Later work found the advantage smaller than first reported. The more interesting result came in 2010, by which time the molecule was called leconotide: injected into a vein of diabetic rats it reduced pain sensitivity at doses that left movement and blood pressure alone, while the largest tolerable intravenous dose of ziconotide did nothing at all. A follow-up in rats with bone tumours found leconotide did little by itself but made morphine roughly fifteen times more effective without adding side effects.
No published study has given leconotide to a person. Amrad, the Melbourne company that licensed the peptide from the University of Queensland, ran an intrathecal safety and tolerability study in cancer patients with severe pain in 2001 and 2002, and a contemporary trade report says the company was pleased with it and was planning a larger phase 2 trial. No paper reporting that trial has appeared in PubMed, no record of it is on ClinicalTrials.gov under any of the molecule's names, and nothing since suggests the programme continued. ChEMBL still records a highest clinical phase of 2 without pointing to a study. So the honest summary is a peptide with a clear mechanism, a promising animal record, and no published human evidence at all.
One naming problem is worth flagging, because it is in the public databases. Both FDA's registry and ChEMBL list 'omega-conopeptide MVIIA' as a synonym for leconotide. MVIIA is ziconotide's peptide, from Conus magus, and it has a different sequence. The sequence those same records hold for leconotide is CVID's, so the synonym is a filing error rather than a sign that the two are the same drug. This site treats them as what they are: two different peptides from two different snails, one approved and one abandoned in early development.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Mechanism of Action
N-type calcium channels sit in the endings of sensory nerves. An incoming signal opens them, calcium floods in, and the nerve releases the transmitters that pass the pain message on. Block the channel and the message is weakened at its first relay. Everything below was measured in cells or animals.
Blocks the N-type (Cav2.2) calcium channel
The peptide plugs the channel's outer mouth. In frog eggs carrying rat N-type channels it blocked current about as strongly as MVIIA, and it discriminated N-type from P/Q-type channels better than earlier omega-conotoxins (PMID 10938268).
Less substance P released in the spinal cord
In slices of rat spinal cord it cut the release of substance P, one of the transmitters sensory nerves use to pass pain signals to the next neuron, and did so at lower concentrations than MVIIA (PMID 11932068).
Lets go of the channel quickly
Recovery after washout was nearly complete for this peptide, partial for MVIIA and least for GVIA (PMID 15166237). Reversibility was the property thought to make it easier to adjust, although a 2013 comparison found the safety margin it bought to be small (PMID 23713957).
The same channels in autonomic nerves
N-type channels also control the nerves that set heart rate and blood vessel tone, which is where the side effects come from. In rabbits, intravenous doses lowered blood pressure and raised heart rate, though the postural reflex recovered faster than after MVIIA (PMID 11090104).
Why a vein might be enough
In diabetic rats, intravenous leconotide reduced heat sensitivity at doses that did not affect movement or blood pressure, while ziconotide given the same way did not (PMID 20002322). The authors read the difference as a wider gap between the pain and the autonomic effects. This has never been tested in a person.
Published Research
The twelve studies below are the published work on this peptide itself, read from their PubMed abstracts on November 4, 2026. None is human: no trial of leconotide has been published. Three titles name the molecule only in their abstracts and are carded under the site's abstract rule, with the naming sentence recorded. Findings in these papers about MVIIA, GVIA, CVIE, CVIF or the single-residue hybrids belong to those molecules, not to this one.
Where it came from: four new peptides from Conus catus
A Queensland group screened the venom of this fish-hunting snail for blockers of N-type calcium channels and named the four they found CVIA to CVID. Of those, CVID preferred N-type channels over P/Q-type ones by the widest margin yet measured in a binding assay, and its fourth loop had a sequence no other omega-conotoxin carried. Against rat N-type channels expressed in frog eggs it was about as potent as MVIIA, the peptide behind ziconotide, and much more potent when the channel's accessory beta subunit was absent. NMR showed its loops held rigidly in place.
Pain relief in rats, and the gap between dose and side effects
Rats with long-running inflammation of one hind paw were given the peptide, then called AM336, into the spinal fluid. It raised their pain thresholds in proportion to the dose, and the doses that caused visible side effects were roughly ten times the ones that relieved pain. MVIIA worked at lower doses but its curve turned down above a point, while its side effects kept increasing, which the authors read as a warning about adjusting it in clinic. In slices of rat spinal cord, both peptides cut the release of substance P, a pain-signalling transmitter, with AM336 the stronger of the two.
Nerve-injury pain in rats, against two other conotoxins and morphine
In rats whose spinal nerves had been tied, a model of nerve-injury pain, spinal injections of CVID (named here as AM-336) relieved sensitivity to light touch at about 0.36 micrograms per kilogram, close to MVIIA, while GVIA needed about a third of that. Morphine needed roughly ten times more than any of the peptides and was the only one of the four to blunt an ordinary heat response. Weighing relief against clumsiness and other behavioural effects, CVID came out with the widest margin of the three peptides.
Given into a vein instead of the spine, in diabetic rats
This is the study the name leconotide belongs to, and the one that changed what the peptide was being developed for. Rats made diabetic with streptozotocin became unusually sensitive to heat. Working out first how much of each drug could be given into a vein without affecting movement or blood pressure, the authors then compared those ceiling doses: leconotide at 2 mg/kg removed about half the extra sensitivity, while the highest tolerable intravenous dose of ziconotide (0.02 mg/kg) did essentially nothing. Adding the potassium channel drug flupirtine, itself ineffective at the dose used, lifted a small dose of leconotide to about 84% reversal; the same combination did nothing for ziconotide. The authors' point was that leconotide seemed usable by an ordinary injection, without a spinal catheter.
Bone cancer pain in rats: little alone, a lot with morphine
Prostate cancer cells were injected into one shin bone of rats, and the growing tumour made the paw on that side sensitive to heat. Intravenous leconotide on its own did almost nothing. Morphine alone worked dose-dependently, needing about 2.4 mg/kg for half the effect; with leconotide added at 20 micrograms per kilogram that fell to about 0.16 mg/kg, a fifteenfold shift, with no increase in side effects measured by open-field activity, rotarod and blood pressure. The authors argued this combination could reach patients with bone metastases who cannot have a spinal catheter. This is a rat study; no trial has tested the combination in people.
A later look: only a marginal advantage over MVIIA
The same nerve-ligation model, now comparing CVID, MVIIA and two hybrids that swap a single residue at position 10. All four reduced touch sensitivity with dose, and all four produced side effects on the rotarod and on a visual rating. CVID's advantage over MVIIA this time was slight, and it did not track how fast the peptides let go of the channel, which had been the proposed explanation. In spinal cord slices, recovery after block depended on how deep the block had been rather than on which peptide caused it. The hybrids impaired coordination less than either parent, which the authors suggested was worth pursuing.
Combined with dexmedetomidine in the spinal fluid
Rats with nerve-ligation pain were given spinal CVID and the sedative dexmedetomidine, separately and together. Each abolished touch sensitivity on its own, CVID at about 0.35 micrograms per kilogram. Together, at two different ratios, they were clearly synergistic: the interaction index was around 0.3 to 0.4, meaning the pair worked at roughly a third of the doses the separate curves predicted. Only dexmedetomidine changed the ordinary heat response. Lower doses of both drugs, the authors suggested, might avoid the toxicity each shows alone.
Under the skin in mice, beside two newer relatives
Three peptides from the same snail, CVID, CVIE and CVIF, were tested on calcium currents in mouse sensory neurons and then injected under the skin of mice with inflamed paws. On the isolated neurons CVID was the weakest of the three. In the animals, CVID and CVIE partly restored normal weight-bearing on the inflamed limb while CVIF did not, and the authors saw no neurological side effects from any of them. They took this as evidence that peptides of this family might work given outside the spinal canal.
Blood pressure and reflexes in rabbits, with MVIIA alongside
N-type channels also sit in the nerves that control the heart and blood vessels, so this study measured what the two peptides do there. On isolated rat tissue CVID and MVIIA blocked nerve-driven responses in the heart and vas deferens about equally, but CVID was the weaker of the two on small mesenteric arteries. Given into a vein of conscious rabbits at 100 micrograms per kilogram, both dropped blood pressure and sped the heart. MVIIA abolished the blood-pressure response to being tilted upright for an hour and a half or more; after CVID that response came back quickly. At the much smaller spinal dose of 3 micrograms per kilogram neither changed circulation or reflexes.
Why the channel's companion subunits matter
N-type channels are built from a pore-forming subunit plus accessory ones whose amounts change in disease, including in pain states. Adding the alpha2delta subunit slowed how fast GVIA, MVIIA and CVID attached to the channel and weakened the block they produced, in frog eggs and, less markedly, in human kidney cells. It sharpened MVIIA's preference for the brain form of the channel but not CVID's. Recovery after washout was the clearest difference between the peptides: almost complete for CVID, partial for MVIIA, least for GVIA. That reversibility is the property later work hoped would make CVID safer to adjust.
A channel in nerve endings that only this peptide blocks
Transmitter release from the nerves feeding the rat submandibular ganglion resists the usual blockers of every known calcium channel type. CVID stopped it; MVIIA did not, although both blocked cloned N-type channels in frog eggs and left L- and R-type channels alone. Swapping in the smaller lysine that CVID carries at position 10, in place of MVIIA's arginine, improved the block. The authors concluded that the channel in these nerve endings is probably an unusual variant of the N-type channel rather than a different type.
What happens to blood-pressure reflexes during simulated blood loss
Seven instrumented rabbits received spinal doses of CVID, MVIIA or dexmedetomidine, then had their venous return gradually restricted to imitate bleeding. Both peptides reduced resting cardiac output by about a fifth at three hours, but only MVIIA lowered resting blood pressure. During the simulated bleed, MVIIA blunted the usual tightening of blood vessels and the rise in heart rate for one to three hours afterwards; the differences from CVID were statistically clear, and the authors judged MVIIA's prolonged effect the one likely to matter clinically. Both peptides left vessels unable to recover once compensation failed, which is why they warned that spinal drugs of this kind may weaken the response to a fall in blood volume.
Side Effects & Contraindications
Reported Side Effects
No human safety data for leconotide have been published. The observations below are from animals, and the species and route are given each time.
Contraindications & Cautions
There is no label and no approved use, so there are no official contraindications. What follows is what the record supports saying.
Legal Status
Leconotide was never approved in any country and its development appears to have stopped.
Frequently Asked Questions
?What is leconotide?
A synthetic copy of a peptide from the venom of the cone snail Conus catus, 27 amino acids long, that blocks N-type calcium channels in nerve endings. It was developed as a treatment for severe pain under the names AM336 and CNSB004, and is also called omega-conotoxin CVID in the research literature.
?Is it the same as ziconotide?
No, although public databases muddle this. Ziconotide is the peptide MVIIA, from Conus magus, 25 residues long, and it is an approved medicine. Leconotide is CVID, from Conus catus, 27 residues, and was never approved. FDA's registry and ChEMBL both list 'omega-conopeptide MVIIA' as a synonym for leconotide, which does not match the sequence they hold for it.
?Has it ever been given to people?
Amrad ran an intrathecal safety and tolerability study in cancer patients with severe pain around 2001 and 2002, and a trade report at the time said the company was encouraged by it. No paper reporting that study is in PubMed and no trial record exists, so there is no usable human evidence and no published dose.
?Why was the intravenous route the interesting part?
Because ziconotide has to be infused into the spinal fluid through an implanted pump, which rules it out for most people. In diabetic rats, leconotide given into a vein reduced pain sensitivity at doses that left movement and blood pressure alone, whereas intravenous ziconotide did not (PMID 20002322). That result is from rats.
?What happened to it?
The published trail stops in 2011. Amrad's pain programme did not produce a reported phase 2 trial, the molecule reached an INN and a ChEMBL phase 2 record, and no sponsor has reported anything since. Nothing in the public record says explicitly why.
?Can it be bought?
It is not a medicine in any country and Grey Peptides does not point to sellers. Anything offered under the name leconotide, AM336 or CVID has no approved standard to be judged against, and the peptide's three disulfide bonds have to be formed correctly for it to do anything at all.
References
- [pubmed] Lewis RJ, et al. "Novel omega-conotoxins from Conus catus discriminate among neuronal calcium channel subtypes." J Biol Chem, 2000;275(45):35335-44. PMID: 10938268.
- [pubmed] Wright CE, et al. "Cardiovascular and autonomic effects of omega-conotoxins MVIIA and CVID in conscious rabbits and isolated tissue assays." Br J Pharmacol, 2000;131(7):1325-36. PMID: 11090104.
- [pubmed] Smith MT, et al. "The novel N-type calcium channel blocker, AM336, produces potent dose-dependent antinociception after intrathecal dosing in rats and inhibits substance P release in rat spinal cord slices." Pain, 2002;96(1-2):119-27. PMID: 11932068.
- [pubmed] Scott DA, et al. "Actions of intrathecal omega-conotoxins CVID, GVIA, MVIIA, and morphine in acute and neuropathic pain in the rat." Eur J Pharmacol, 2002;451(3):279-86. PMID: 12242089.
- [pubmed] Adams DJ, et al. "Omega-conotoxin CVID inhibits a pharmacologically distinct voltage-sensitive calcium channel associated with transmitter release from preganglionic nerve terminals." J Biol Chem, 2003;278(6):4057-62. PMID: 12441339.
- [pubmed] Blake DW, et al. "Cardiovascular reflex responses after intrathecal omega-conotoxins or dexmedetomidine in the rabbit." Clin Exp Pharmacol Physiol, 2003;30(1-2):82-7. PMID: 12542459.
- [pubmed] Mould J, et al. "The alpha2delta auxiliary subunit reduces affinity of omega-conotoxins for recombinant N-type (Cav2.2) calcium channels." J Biol Chem, 2004;279(33):34705-14. PMID: 15166237.
- [pubmed] Blake DW, et al. "Synergy between intrathecal omega-conotoxin CVID and dexmedetomidine to attenuate mechanical hypersensitivity in the rat." Eur J Pharmacol, 2005;506(3):221-7. PMID: 15627431.
- [pubmed] Kolosov A, et al. "CNSB004 (Leconotide) causes antihyperalgesia without side effects when given intravenously: a comparison with ziconotide in a rat model of diabetic neuropathic pain." Pain Med, 2010;11(2):262-73. PMID: 20002322.
- [pubmed] Kolosov A, et al. "Intravenous injection of leconotide, an omega conotoxin: synergistic antihyperalgesic effects with morphine in a rat model of bone cancer pain." Pain Med, 2011;12(6):923-41. PMID: 21539704.
- [pubmed] Jayamanne A, et al. "Spinal actions of ω-conotoxins, CVID, MVIIA and related peptides in a rat neuropathic pain model." Br J Pharmacol, 2013;170(2):245-54. PMID: 23713957.
- [pubmed] Sadeghi M, et al. "Novel ω-conotoxins from C. catus reverse signs of mouse inflammatory pain after systemic administration." Mol Pain, 2013;9:51. PMID: 24139484.
- [pubmed] Schroeder CI, et al. "N-type calcium channel blockers: novel therapeutics for the treatment of pain." Med Chem, 2006;2(5):535-43. PMID: 17017994.
- [pubmed] Adams DJ, et al. "Analgesic conotoxins: block and G protein-coupled receptor modulation of N-type (Ca(V) 2.2) calcium channels." Br J Pharmacol, 2012;166(2):486-500. PMID: 22091786.
- [pubmed] Deer T, et al. "Future directions for intrathecal pain management: a review and update from the interdisciplinary polyanalgesic consensus conference 2007." Neuromodulation, 2008;11(2):92-7. PMID: 22151040.
- [pubmed] Bu W, et al. "Development of a method for the direct analysis of peptide AM336 in monkey cerebrospinal fluid using liquid chromatography/electrospray ionization mass spectrometry with a mixed-function column." Rapid Commun Mass Spectrom, 2003;17(21):2394-8. PMID: 14587085.
- [pubmed] Schroeder CI, et al. "Effects of Lys2 to Ala2 substitutions on the structure and potency of ω-conotoxins MVIIA and CVID." Biopolymers, 2012;98(4):345-56. PMID: 23193599.
- [other] US FDA Global Substance Registration System, substance LECONOTIDE (UNII 2P1P5JB93S, protein), read November 4, 2026: 27 residues CKSKGAKCSKLMYDCCSGSCSGTVGRC with a C-terminal cysteinamide and three disulfide bonds (1-16, 8-20, 15-27); names leconotide [INN] and 'omega-conopeptide MVIIA'; codes INN 8095, CAS 247207-64-3, NCI Thesaurus C166586, ChEMBL CHEMBL2108419. The MVIIA synonym does not match the sequence in this record, which is omega-conotoxin CVID's. https://gsrs.ncats.nih.gov/ginas/app/beta/substances/2P1P5JB93S
- [other] ChEMBL molecule CHEMBL2108419 (LECONOTIDE), read November 4, 2026: molecule type Protein, synonyms Leconotide, Leconotida and 'Omega-conopeptide mviia', highest clinical phase recorded 2, with no trial or indication record attached. https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL2108419/
- [registry] ClinicalTrials.gov API v2, searched November 4, 2026 for leconotide, AM336, AM-336 and omega-conotoxin CVID: no study record of any kind. https://clinicaltrials.gov/
- [other] US FDA, Drugs@FDA and the drug label endpoint (openFDA), searched November 4, 2026: no application and no label record for leconotide, AM336 or CNSB004.
- [other] "Cone snail proving to be companies' best friend", Life Scientist (labonline.com.au), February 26, 2002, read November 4, 2026: Amrad Corporation held worldwide rights to AM336, a synthetic form of CVID discovered at the University of Queensland, and had completed a phase I/II intrathecal study in cancer patients with severe chronic pain, dosed over 12 days to assess safety and tolerability, with a larger phase 2 study planned and an FDA meeting set for March 2002. The report gives no amounts and no outcome figures. https://www.labonline.com.au/content/life-scientist/news/cone-snail-proving-to-be-companies-best-friend-1102532228
Sources & Citations
The twelve studies carded above and the four References-only papers were read from their PubMed records on November 4, 2026. Sequence, disulfide bonds, codes and the INN come from FDA's Global Substance Registration System (UNII 2P1P5JB93S); the clinical phase and synonym list from ChEMBL (CHEMBL2108419); the absence of trials from the ClinicalTrials.gov API; United States status from Drugs@FDA and the openFDA label endpoint, all read the same day. The 2001-2002 intrathecal study is reported only in a Life Scientist news article of February 26, 2002, which is cited as a news source and not as trial evidence. Grey Peptides sells nothing and links to no vendor.
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