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DSIP peptide (delta sleep-inducing peptide): research and forms

DSIP (delta sleep-inducing peptide) is a nine-residue neuropeptide (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) isolated from rabbit cerebral venous blood. It is studied for slow-wave (delta) EEG activity, stress responses and withdrawal syndromes, with mixed results and no identified receptor. PrymaLab supplies it as DSIP 5mg and DSIP 10mg vials, a DSIP 10mg Nasal Spray and a preloaded pen for research use.

  • Sequence: WAGGDASGE (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu), nine residues; molecular weight 848.8 g/mol; INN emideltide.
  • Class: hypothalamic neuropeptide with no identified receptor; its mechanism is unresolved after nearly five decades of study.
  • Studied for: delta EEG activity in rabbits, rats and humans; stress and thermoregulation; alcohol and opiate withdrawal; chronic pain.
  • What the literature measured: delta and spindle EEG patterns in rabbits, sleep structure in a small insomnia series, and withdrawal symptoms in inpatients (table below).
  • Storage: lyophilized vial frozen at -20°C and protected from light (the N-terminal tryptophan photo-oxidizes); solution at 2 to 8°C.
  • Forms and sizes at PrymaLab: DSIP 5mg vial, DSIP 10mg vial, DSIP 10mg Nasal Spray, DSIP 3ml pen, 10mg.
  • CAS number: 62568-57-4.

For vial work the peptide reconstitution calculator converts vial size and diluent volume into concentration; for the spray format, see the guide on whether peptide nasal sprays work.

DSIP is a nine-amino-acid neuropeptide isolated from rabbit brain blood in 1974. In some animal studies it raises delta (slow-wave) EEG activity; in others it shows no effect, or the opposite. This research-use-only reference lays out both sides of that split literature, and the fact that its receptor and mechanism have never been identified.

Research-use-only disclaimer: DSIP supplied as a research chemical is intended strictly for in-vitro and laboratory research use and is not intended for human or veterinary use in that context. Every finding below is drawn from cell, animal, or human-imaging models and is described in hedged, mechanistic terms. Nothing here is medical advice.

TL;DR

DSIP is a nonapeptide (sequence WAGGDASGE) isolated from rabbit cerebral venous blood in 1974. In some animal studies it increases slow-wave sleep and total sleep time; in others it shows no effect, and one human study linked higher endogenous DSIP to less slow-wave and REM sleep. Its receptor and mechanism remain unidentified. It is a research compound, not a sleep drug.

Structure: nine residues, Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu (WAGGDASGE); isolated 1974.

Sleep, positive: some rat studies report more slow-wave sleep and longer total sleep.

Sleep, negative: other studies report no effect; one human study tied higher DSIP to less slow-wave and REM sleep.

Mechanism: no receptor, gene, or precursor identified. Unresolved.

Status: research-use-only; no established human effect.

What Is DSIP?

DSIP is a nonapeptide the Schoenenberger-Monnier group in Switzerland isolated in 1974 from the cerebral venous blood of rabbits held in an induced sleep state. Its amino-acid sequence is Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu (WAGGDASGE). The name describes what the discoverers observed, delta-wave sleep, not a proven mechanism. It is studied among cognitive, sleep, and mood research peptides.

What Does DSIP Do to Sleep in Animal Studies?

In the early work, infusing DSIP into recipient animals produced spindle and delta EEG patterns and reduced motor activity. A 1988 rat study reported that DSIP increased the share of slow-wave sleep and lengthened total sleep time, and linked it to sleep-related growth hormone release, per the PNAS report (1988). Those results are why DSIP entered the sleep-research literature.

The honest headline: DSIP results do not replicate cleanly. The same peptide reads as sleep-promoting in some models and sleep-neutral or sleep-suppressing in others, which is the finding a research audience should carry forward.

Why Is the Evidence Mixed?

This is the part most product pages skip. Injecting DSIP into the dorsal raphe nucleus of rats produced no sleep effect in one study, and a human study of natural DSIP rhythms found that higher circulating levels tracked with less slow-wave and REM sleep, not more, as reported in the diurnal-rhythm study (1994). For a research audience, that inconsistency is the key result.

Table 1. What DSIP studies have reported
Study / modelReported result
Recipient rabbits, early workDelta and spindle EEG; reduced motor activity
Rat, slow-wave sleep (1988)Increased slow-wave sleep and total sleep time
Rat, dorsal-raphe injectionNo sleep effect
Human, endogenous DSIP rhythm (1994)Higher DSIP tracked with less slow-wave and REM sleep
"DSIP is a useful reminder that a peptide's name is not its mechanism. It was named for delta sleep in 1974, and fifty years later we still cannot point to its receptor. For a researcher, that open question is exactly what makes it worth studying carefully rather than overselling." — Michael Phelps, Founder & Peptide Research Specialist, PrymaLab

Breakdown in blood, and why analogues behaved differently

One reason DSIP results vary between laboratories may be how quickly the peptide is destroyed in blood. Graf, Saegesser and Schoenenberger examined the biostability of DSIP and two analogues in blood, asking whether rates of inactivation contribute to variable effects in vivo (Graf et al. 1987). Incubating DSIP in human or rat blood released products with gel filtration retention times equivalent to tryptophan, and the formation of these products depended on temperature, time and species (Graf et al. 1987).

The analogues behaved differently. Iodinated N-tyrosyl DSIP and a phosphorylated form, N-Tyr-P-DSIP, degraded more slowly and, unlike DSIP, formed complexes. An excess of unlabelled material did not displace the radioactivity, which pointed to non-specific binding or aggregation, not a specific binding site (Graf et al. 1987). The authors concluded that DSIP vanishes rapidly from the circulation because it is degraded, while slower degradation combined with complex formation lets the analogues persist longer in apparently intact form (Graf et al. 1987). Whether that explains the sometimes stronger and more consistent effects reported for DSIP analogues was left open.

The finding sits beside the 2006 review's observation that certain artificial DSIP analogues, but not DSIP itself, promoted slow-wave sleep in early rabbit and rat studies (Kovalzon et al. 2006). Together the two papers suggest that differences in stability, as well as in activity at some target, could separate DSIP from its analogues in living animals. No study among the references here has tested that directly.

What Is DSIP's Mechanism?

Unknown. No DSIP receptor, gene, or precursor protein has been definitively identified, even decades after its discovery. That gap is unusual for a named neuropeptide and it is the main reason DSIP stays a research subject rather than a developed compound. Any page that states a confident mechanism is going beyond the evidence.

What Else Has DSIP Been Studied For?

Beyond sleep, DSIP has been examined for stress and neuroprotection endpoints. A 2021 rat study reported improved motor-function recovery after focal stroke, per the Molecules report (2021). These are single preclinical findings, not established effects, and none of them support human use.

How is research-grade DSIP characterized?

For reproducible sleep-EEG and neuro work, identity and purity are what matter. Research-grade DSIP is typically confirmed by reversed-phase HPLC for purity and mass spectrometry for identity, handled cold, and supplied for laboratory use only. At PrymaLab, research peptides are tested in PrymaLab's own laboratory (RP-HPLC purity, LC-MS identity), and certificates can be checked at https://prymalab.net/testing/verify/. No specific lot data are asserted in this general reference.

What the DSIP studies measured

DSIP has been given to rabbits, rats and human volunteers since the 1970s, almost always by intravenous infusion. The table lists the main studies by design and what they reported; amounts are not reproduced. The literature disagrees with itself, and research-grade DSIP is supplied for laboratory use only.

StudyModel or subjectsRoute and designReported outcome
Schoenenberger and Monnier, PNAS 1977 (characterization of the nonapeptide)RabbitsIntraventricular infusion into the brainDelta and spindle EEG patterns increased specifically; the finding that named the peptide
Schneider-Helmert, European Neurology 1984 (summary of the DSIP insomnia studies)Patients with chronic insomniaIntravenous injection; single and four consecutive administrationsSleep improved after single injections; sleep structure normalized after four consecutive administrations
Dick and colleagues, European Neurology 1984Patients in alcohol or opiate withdrawalIntravenous DSIP, repeated injections; 107 inpatients, 47 in alcohol and 60 in opiate withdrawalSymptoms resolved or improved markedly in 97% of the opiate and 87% of the alcohol withdrawal patients
Kovalzon and Strekalova, Journal of Neurochemistry 2006 (review)Rodent, rabbit and human studies over three decadesRoutes vary widely between the studies reviewedSleep effects inconsistent between laboratories; no receptor identified

Two things stand out. First, nearly all of the controlled work used intravenous or intraventricular infusion. Second, the positive human findings cluster in the first half of the 1980s and come from two separate teams, the Basel laboratory that isolated the peptide and the clinicians who reported the withdrawal series, with no later replication at scale, which is why the 2006 review still called the peptide an unresolved riddle. Later animal work on stress, thermoregulation and pain used a wider range of routes, and those results are at least as mixed as the sleep data.

DSIP nasal spray vs vial

The same nonapeptide is sold in three formats, and the differences are practical rather than chemical.

PropertyLyophilized vialNasal sprayPreloaded pen
What it containsDSIP 5mg or DSIP 10mg of freeze-dried powderDSIP 10mg Nasal Spray, pre-dissolved in a metered spray bottleDSIP preloaded pen holding 10 mg in 3 ml of solution (10/3 mg/ml)
PreparationDissolved in a suitable diluent; concentration set by the diluent volumeNone; metered sprayNone; the solution is ready
Route in the published studiesIntravenous infusion in the human studies aboveIntranasal, across the nasal mucosa; the controlled DSIP studies did not use this route, so spray data are extrapolatedNo published studies of this format
StoragePowder frozen at -20°C, protected from light; solution refrigerated at 2 to 8°CRefrigerated, protected from lightRefrigerated, protected from light

The vial is the most flexible format: concentration is mass divided by volume (5 mg in 1 ml gives 5 mg/ml), and the peptide reconstitution calculator converts any vial size and diluent volume into concentration. The spray and the pen remove the mixing step at the cost of a fixed concentration. Because DSIP's tryptophan photo-oxidizes, every format is kept in the dark. How much of a 9-residue peptide crosses the nasal mucosa is covered in the guide on whether peptide nasal sprays work.

Frequently Asked Questions

What is DSIP peptide?

DSIP, delta sleep-inducing peptide, is a nine-amino-acid neuropeptide (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) first isolated from the cerebral venous blood of rabbits by the Monnier group in Basel. It was named for raising delta (slow-wave) EEG activity, an effect later studies did not always reproduce. Its receptor has never been identified, and it is supplied for research use only.

Does DSIP actually work for sleep?

The evidence is split. Some rabbit and rat studies report more delta EEG activity after intravenous DSIP; others report no change or the opposite. Small human studies from one group in the 1980s reported better sleep in insomnia patients, but the work was never replicated at scale, and a 2006 review in the Journal of Neurochemistry still called the peptide an unresolved riddle.

How were the DSIP studies designed?

The original rabbit and human studies used single intravenous or intraventricular infusions, and the human insomnia and withdrawal series were small and unreplicated. Later animal work on stress and pain used a wider range of routes. No regimen has been validated and DSIP is supplied for research only.

How does DSIP nasal spray compare to the vial?

Both contain the same nonapeptide. The vial is freeze-dried powder that is dissolved in a diluent, so the concentration is set by the researcher; the spray is pre-dissolved in a metered bottle at a fixed concentration and needs no mixing. The controlled DSIP studies used intravenous infusion, so no trial data exist for the intranasal route.

How is DSIP reconstituted?

Concentration is mass divided by volume: a 5 mg vial dissolved in 1 ml gives 5 mg/ml, and a 10 mg vial in 2 ml gives the same concentration. The diluent is added slowly down the glass and the vial swirled, not shaken. The solution is refrigerated at 2 to 8°C and kept in the dark, because DSIP's tryptophan residue photo-oxidizes.

Does DSIP reliably improve sleep?

No. Animal and human findings are contradictory, and the mechanism is unknown. The evidence does not support a reliable sleep effect.

What is DSIP's amino-acid sequence?

Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu (WAGGDASGE), a nine-residue peptide.

What is DSIP's mechanism of action?

Unknown. No receptor, gene, or precursor has been definitively identified, which is the defining open question in the DSIP literature.

Is DSIP approved for human use?

No. DSIP reference material is for laboratory research only. It is not a sleep aid or a drug.

References

  1. Schoenenberger GA, Monnier M. Characterization of a delta-electroencephalogram (sleep)-inducing peptide. Proc Natl Acad Sci USA. 1977.
  2. Evidence for a role of delta sleep-inducing peptide in slow-wave sleep and sleep-related growth hormone release in the rat. Proc Natl Acad Sci USA. 1988;85(10):3653–3657. PNAS
  3. Diurnal rhythm of plasma DSIP in humans and its relation to slow-wave and REM sleep. PubMed. 1994. PMID:8175965
  4. Delta sleep-inducing peptide and motor-function recovery after focal stroke in rats. Molecules. 2021;26(17):5173. MDPI

Final disclaimer: This article is an educational research reference. DSIP is sold and studied for laboratory research use only and is not approved by any regulatory authority for human or veterinary use. Statements have not been evaluated by the FDA. Nothing here should be interpreted as medical advice.

Mechanistic descriptions are observations from animal and human-imaging models that may not generalize; DSIP findings are notably inconsistent. Always verify the legal status of any research compound in your jurisdiction before purchase or use.

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For laboratory and research use only. Not for human consumption. PrymaLab sells to qualified researchers and licensed laboratories only. Not a drug, food or cosmetic. Not for human consumption. This product has not been evaluated by the Food and Drug Administration and is not intended to diagnose, treat, cure or prevent any disease.