pe
pep-10516 v1 CC-BY-SA-4.0

Vasotocin: natural bonding and contraction hormone found in fish and other animals

A small hormone from non-mammalian animals (fish, frogs, birds, reptiles) that drives womb contractions, water balance, and social bonding; used only as a lab research tool.

statussynthesized targetOXTR length8 aa refs2
snapshot sparse 15% confidence
Class
Neurohypophysial neuropeptide (fish-derived)
Status
No approved therapeutic status identified
Main caveat
No functional bioactivity, animal efficacy, or human evidence is attached to this card. Sequence and gene-expression context from grass puffer only.
status 4 / 5
prediction metrics boltz-2 2.2.1
ipTM0.984
pTM0.921
avg pLDDT84.8
ranking score0.875
STRUCTURE · PEP-10516 × OXTR
ranking0.875
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
boltz-2 2.2.1 · mmCIF ↓ download
sequence8 aa
158
CYIQNCPR
in the news 2 articles
overview readme

What this is

Vasotocin (also called arginine vasotocin, or AVT) is a nine-residue neurohypophysial hormone found throughout non-mammalian vertebrates — fish, amphibians, reptiles, and birds — where it serves roles broadly equivalent to both oxytocin and vasopressin in mammals. It acts primarily at the oxytocin receptor (OXTR), a class A G-protein-coupled receptor, and drives a range of effects including smooth-muscle contraction, water balance, and social behavior. The sequence stored here, CYIQNCPR, is the eight-residue backbone; the natural peptide is nine residues (CYIQNCPRG with a C-terminal glycinamide) and carries a disulfide bridge between the cysteines at positions 1 and 6 that is essential for its three-dimensional ring structure and receptor binding — neither the terminal glycinamide nor the disulfide bond is encoded in the raw stored sequence (Möller and colleagues, 2007; Motohashi and colleagues, 2008).

History

Vasotocin was characterized across a wide range of non-mammalian vertebrate species long before the molecular era. Motohashi and colleagues (2008) cloned and sequenced the neurohypophysial hormone genes — including the vasotocin gene — from the grass puffer Takifugu niphobles, documenting its gene structure and seasonal changes in expression during the spawning period. The same study situated vasotocin within the broader classification of neurohypophysial hormones: vertebrate species typically carry one vasopressin-like peptide and one oxytocin-like peptide, and in non-mammalian vertebrates vasotocin occupies the vasopressin-like slot. Möller and colleagues (2007), in work characterizing a related conopressin from cone snail venom, provided a cross-species alignment confirming that CYIQNCPRG is the canonical vasotocin sequence found in non-mammalian vertebrates.

What it does

Vasotocin acts at oxytocin and vasopressin receptors to regulate two broad domains: reproductive physiology and social behavior. On the physiological side, it stimulates smooth-muscle contraction in the uterus and related tissues, and plays roles in water and ion balance in aquatic species. Motohashi and colleagues (2008) documented that vasotocin gene expression in the grass puffer changes markedly across the spawning season, consistent with a reproductive coordination role. On the behavioral side, vasotocin has been shown to modulate social and sexual behavior across a broad range of vertebrate species, with effects including pair-bond formation, aggression, and communication (Motohashi and colleagues, 2008).

Evidence

  • Human: No human clinical trials have been conducted with this peptide.
  • Animal: Vasotocin's behavioral and reproductive effects have been characterized in fish, amphibians, and other non-mammalian vertebrates. Motohashi and colleagues (2008) documented gene expression changes in grass puffer across the spawning season. Vasotocin has been identified biochemically in species including cartilaginous fishes and amphibians, confirmed through chromatographic and pharmacological methods.
  • In vitro: Vasotocin binds both vasopressin-type and oxytocin-type receptors. The Möller and colleagues (2007) cross-species alignment places it within the vasopressin/oxytocin superfamily alongside conopressins, diuretic hormones, and related neuropeptides, all sharing the conserved disulfide-bridged nonapeptide scaffold.

Known effects

  • Smooth-muscle contraction (uterotonic) — Preclinical; well established in non-mammalian vertebrate models
  • Social and sexual behavior modulation — Preclinical; documented across fish, amphibian, and reptile species (Motohashi and colleagues, 2008)
  • Water and ion balance — Preclinical; vasopressin-like osmoregulatory role in aquatic vertebrates
  • Spawning coordination — Preclinical; gene expression changes during reproductive season in grass puffer (Motohashi and colleagues, 2008)

Regulatory status

  • US: Not approved by the FDA. No IND or NDA on record. Research-use status.
  • EU: Not approved by the EMA.
  • WADA: No specific listing; would fall under general peptide hormone provisions if used in sport contexts.

Related peptides

Vasotocin belongs to the neurohypophysial nonapeptide superfamily. Its closest mammalian counterparts are oxytocin and vasopressin (arginine vasopressin), which arose from a common ancestral gene. Related platform cards include oxytocin, the mammalian oxytocin-receptor agonist that shares the same core ring structure and C-terminal amide, and vasopressin (arginine vasopressin), the mammalian vasopressin-family counterpart. Möller and colleagues (2007) described conopressins — venom-derived vasotocin/oxytocin-related peptides from cone snails — as a further branch of the same superfamily.

Hypotheses4 directions▾ collapse

Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.

openupdated 2026-06-05

Does vasotocin trigger only some of the oxytocin receptor's effects, potentially leaving out the ones that cause side effects?

If vasotocin preferentially activates brain-based bonding pathways without triggering uterine contractions, it could become the basis for safer social-behavior medicines, particularly important for pregnant women or people with cardiovascular sensitivities.

The hypothesis
Vasotocin may act as a partial rather than full OXTR agonist in mammalian systems, because the R8 substitution and absent glycinamide alter the receptor's intracellular coupling geometry relative to oxytocin, shifting the balance between Gq-mediated calcium mobilization and beta-arrestin recruitment.
Why it’s plausible
OXTR is known to signal through both Gq (calcium, uterine contraction) and beta-arrestin (internalization, ERK). Structural differences at the C-terminus of OXTR-binding peptides can shift this balance. Vasotocin differs from oxytocin at two positions that contact the receptor's extracellular loops, and biased agonism at OXTR has been proposed as a route to separating desired (prosocial) from undesired (contractile) effects. The high ipTM does not distinguish full from partial or biased agonism.
Why it matters
If vasotocin is a naturally biased OXTR agonist favoring one signaling arm, it could separate prosocial CNS effects from peripheral uterotonic effects, a long-sought therapeutic split.
Plausibility.60
Novelty.60
Impact.75
Basis · grounding1 paper · 2 computed/notes
[1]
sequenceR8 (vasotocin) vs. L8 (oxytocin) and absence of glycinamide alter C-terminal contacts with OXTR extracellular loops involved in coupling geometry
[2]
structureHigh ipTM 0.9835 confirms tight binding but is agnostic to downstream signaling pathway engaged
[3]
paper
Vasotocin acts in non-mammalian vertebrates on both social behavior and smooth-muscle contraction, but relative potency across these readouts compared to oxytocin is uncharacterized at the molecular level
doi: 10.1016/j.ygcen.2007.07.009
openupdated 2026-06-05

Could chemists use vasotocin's ring structure as a scaffold to build a tougher, more durable hormone-mimicking medicine?

Hormone peptide drugs are quickly broken down in the body. If vasotocin's compact ring can be locked into a double-constrained shape, it could become a stable pill or injection that treats conditions like uterine dysfunction or social disorders without needing repeated dosing.

The hypothesis
The disulfide-constrained ring of vasotocin is a privileged scaffold for generating bicyclic or stapled analogs that retain high OXTR affinity while gaining protease resistance superior to both oxytocin and vasopressin, because the existing ring pre-organizes the binding conformation and a second constraint at the C-terminus would further reduce entropic cost of binding.
Why it’s plausible
Disulfide-bridged cyclic peptides are inherently more proteolytically stable than linear peptides, but the disulfide itself is redox-labile in vivo. Engineering a second covalent constraint (lactam bridge, hydrocarbon staple, or thioether) at the C-terminal region of vasotocin's 8-residue frame could produce a bicyclic molecule that is both stable and conformationally pre-organized, reducing the entropic penalty of receptor binding and potentially increasing potency beyond the already high ipTM baseline.
Why it matters
Vasotocin's compact, high-affinity ring is an ideal template for next-generation stable bicyclic OXTR agonists suitable for systemic or oral delivery.
Plausibility.65
Novelty.55
Impact.60
Basis · grounding1 paper · 2 computed/notes
[1]
paper
Disulfide confirmed by reduction/alkylation mass spectrometry; mass increase of 116.05 Da from two carbamidomethylated cysteines establishes the ring
doi: 10.1042/bj20061480
[2]
structureipTM 0.9835 shows the 8-residue ring already achieves near-perfect OXTR interface confidence, establishing a strong starting affinity for engineering
[3]
sequenceCYIQNCPR is only 8 residues; short enough that a second bridge would convert it to a true bicyclic peptide with minimal added molecular weight
openupdated 2026-06-05

Could a hormone from fish and birds work better than human oxytocin in the brain to help people with social difficulties?

If true, people with autism spectrum disorder or social anxiety might benefit from a new class of medicines that activates the bonding receptor differently, especially if current oxytocin-based treatments continue to show inconsistent results.

The hypothesis
Vasotocin, by acting at OXTR in the central nervous system, could modulate mammalian prosocial and stress-buffering behaviors in a manner comparable to oxytocin but with a distinct receptor-engagement profile due to R8, making it a candidate scaffold for autism spectrum disorder or social anxiety pharmacology where intranasal oxytocin trials have shown mixed results.
Why it’s plausible
OXTR activation in limbic circuits underlies oxytocin's prosocial effects. Vasotocin drives analogous social behaviors (pair bonding, parental care) across non-mammalian vertebrates via the same receptor. Given the high predicted OXTR affinity and the R8 difference from oxytocin, vasotocin may produce a subtly different receptor signaling profile (biased agonism) that could be more or less efficacious in CNS applications where intranasal oxytocin has been inconsistent.
Why it matters
Opens a non-oxytocin OXTR agonist scaffold for CNS indications where oxytocin itself has failed to show consistent benefit in trials.
Plausibility.55
Novelty.60
Impact.70
Basis · grounding1 paper · 2 computed/notes
[1]
paper
Vasotocin drives social and reproductive behaviors in non-mammalian vertebrates via OXTR-homologous receptors, establishing its CNS-relevant functional profile
doi: 10.1016/j.ygcen.2007.07.009
[2]
structureipTM 0.9835 supports strong OXTR engagement, a prerequisite for CNS OXTR agonism
[3]
sequenceR8 vs. L8 difference from oxytocin could yield different receptor conformation upon binding, relevant to biased signaling hypotheses
openupdated 2026-06-05

Does swapping one building block between vasotocin and oxytocin change how tightly the peptide grips its receptor?

If R8 is a key binding booster, chemists could add it to synthetic oxytocin-like drugs to make them stick to the receptor longer, potentially needing lower doses with fewer side effects.

The hypothesis
The arginine at position 8 (R8) of vasotocin, absent in oxytocin (which carries leucine at that position), creates an electrostatic contact with an acidic residue in the OXTR orthosteric pocket that contributes to the unusually high predicted binding confidence, and substituting R8 with leucine will measurably reduce affinity.
Why it’s plausible
Oxytocin carries leucine at position 8 (CYIQNCPLG) whereas vasotocin carries arginine (CYIQNCPR). The boltz-2 prediction yields a near-perfect ipTM of 0.983 for vasotocin at OXTR. If R8 forms a salt bridge within the receptor pocket, it would explain why a non-mammalian peptide binds OXTR so well despite evolutionary distance, and would identify R8 as an affinity-enhancing residue.
Why it matters
Position 8 arginine could be incorporated into next-generation OXTR agonist designs to boost binding affinity beyond that of natural oxytocin.
Plausibility.70
Novelty.50
Impact.55
Basis · grounding1 paper · 2 computed/notes
[1]
sequencePosition 8 is R (arginine) in vasotocin CYIQNCPR versus L (leucine) in oxytocin CYIQNCPLG; arginine carries a positive charge at physiological pH
[2]
structureipTM 0.9835 is exceptionally high, suggesting a particularly well-defined interface that may reflect specific contacts beyond the conserved ring
[3]
paper
Disulfide presence confirmed by DTT reduction/alkylation mass shift, validating the ring-constrained structure that positions all sidechains for receptor contact
doi: 10.1042/bj20061480
details expand to inspect
full evidence table2 metrics
metricvaluetool
ipTM 0.9835274815559387 boltz-2
ranking score 0.8751110434532166 boltz-2
3-letter notation
Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Arg
recipeboltz-2 2.2.1
parametervalue
modelboltz-2 2.2.1
weights
hardwarevast_v100_32gb
mlx version
python
random seed1
msa strategycolabfold_local
runtime
predicted by
predicted at2026-05-22
citationbibtex
peptidemodel (2026). Vasotocin: natural bonding and contraction hormone found in fish and other animals (pep-10516, v1). PeptideModel. https://peptidemodel.com/card/pep-10516
@peptide{pep10516,
  sequence = {CYIQNCPR},
  target   = {oxtr},
  author   = {peptidemodel},
  year     = {2026},
  status   = {synthesized}
}
related peptides 2 by signal overlap
clinical trials 0 trials · checked 2026-05-09
0
no registered clinical trials as of 2026-05-09; we'll re-check periodically
references 2 papers
discussion no comments
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