DSIP Research, Specifications & Scientific Information

Introduction

DSIP is a nine-residue peptide that was isolated in 1977 by an unusual experiment: blood was dialysed out of the cerebral venous circulation of rabbits while a thalamic region was being electrically stimulated, and the dialysate was fractionated until a single nonapeptide could be shown to alter the electroencephalogram of recipient animals ^[1]. The sequence — Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu — was confirmed by synthesis a year later ^[2].

Nearly fifty years on, no receptor for it has been isolated, no gene, and no precursor protein. A 2006 review in the Journal of Neurochemistry is titled, accurately, "a still unresolved riddle", and argues that the original hypothesis about the peptide's function is extremely poorly documented ^[13]. The clinical literature is small, dates almost entirely from the 1980s, and points in more than one direction: early positive reports were followed by two double-blind studies whose authors concluded against meaningful benefit ^{[9, 11]}.

This page is written around that record rather than around the compound's reputation.

What Is DSIP?

DSIP is a linear nonapeptide, WAGGDASGE in single-letter code, with free N- and C-termini, no disulfide bridge and no other modification. It carries the International Nonproprietary Name emideltide, which is the designation to search under in chemical and regulatory registers where the acronym alone is ambiguous.

It is a peptide of natural origin in the sense that it was isolated from an animal before it was synthesised — but that origin has never been closed off. No gene encoding it has been found and no precursor protein identified, and immunochemical material resembling it is distributed in tissues that do not fit the function originally proposed for it ^[13]. Whether the molecule that was purified in Basel is the molecule that does the work in the intact animal remains an open question in the primary literature, not a settled one.

It has not been approved by the U.S. Food and Drug Administration for any indication. It was never brought to market in any jurisdiction, no marketing application for it is on record in the United States, and no study of it is registered on ClinicalTrials.gov. What exists is a closed body of research, mostly from 1977 to 1992, with occasional reviews since.

The compound's structure places it nowhere in particular. It does not belong to any established peptide family — a point made explicitly in the 2006 review, which notes that the sequence differs from any known representative of the recognised families ^[13]. For a peptide of biological origin that is unusual, and it is part of why the field stalled: there was no neighbouring pharmacology to borrow tools from.

DSIP Specifications

DSIP is a linear nonapeptide with free N- and C-termini and no disulfide bridge, no amidation and no other post-translational modification. Its composition is unusual for a peptide of biological origin: three of nine residues are glycine, two are alanine, and there is exactly one aromatic residue, the N-terminal tryptophan. It carries two acidic side chains — aspartate at position 5 and the C-terminal glutamate — and no basic residue at all, so it is strongly acidic and net negatively charged at physiological pH. The original chemical characterisation established that activity resides in the alpha-aspartyl peptide and not in its beta-aspartyl isomer, which is a purity question rather than a formulation one and is not resolvable from a molecular formula. The identifiers here are the records held by PubChem (CID 68816), which carries CAS registry number 62568-57-4 and FDA/NCATS UNII code YN28Z5YZ73; the substance also holds the International Nonproprietary Name emideltide. Any figure on this page is a reference value: the certificate of analysis supplied with a laboratory order is the record for a given lot.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does DSIP Work?

No mechanism is established, and the most useful thing this section can do is be precise about the shape of the gap.

What is missing is not detail but the foundation. There is no identified receptor, so there is no binding assay, no affinity constant, no antagonist and no knockout. There is no identified gene, so there is no expression map and no way to ask where or when the peptide is made. There is no identified precursor protein, so the processing pathway that would produce a nonapeptide from a larger chain is unknown. The 2006 review sets out all three absences together and treats them as the reason the field's central hypothesis could never be tested properly ^[13].

What does exist is a set of observations at the level of the whole animal, a proposal from the 1980s that the peptide modulates adrenergic transmission — which the contemporary review of the field described as remaining to be established ^[8] — and an observation from clinical work in withdrawal syndromes that the effects reported there were reversed by naloxone in the underlying animal experiments, which led to a suggestion of opioid receptor involvement ^[6]. That suggestion has not been substantiated by direct receptor work in the four decades since.

The 2006 review proposes an alternative worth stating, because it reframes everything else: that a different, related peptide — not the nonapeptide itself — may be responsible for at least part of the immunoreactivity and the biological activity attributed to DSIP ^[13]. If that is right, much of the older literature is measuring something other than what it names.

DSIP Mechanism of Action

Animal research

The peptide's name is an acronym of delta sleep-inducing peptide, the descriptive name given by the group that isolated it, after the electroencephalographic pattern it produced in rabbits ^[1]. The name was a description of one experimental observation, not a conclusion about physiology, and the distinction has been lost in most secondary accounts of the compound.

The original characterisation. A peptide that enhanced slow-wave (delta) and spindle patterns in the electroencephalogram after intraventricular infusion was isolated from rabbits and sequenced. The compound was then compared, under double-blind conditions in a total of 58 rabbits including controls, against five of its own possible metabolic products (fragments 1–8, 2–9, 2–8, 1–4 and 5–9), two nonapeptide analogues with amino acid substitutions, and a related tripeptide. Electroencephalographic leads from neocortex and archicortex were Fourier-transformed and analysed by computer. Only the intact nonapeptide produced the delta and spindle pattern ^[1].

Synthesis and confirmation. The following year the synthetic peptide was tested the same way in 61 rabbits at 6 nmol/kg by intraventricular infusion. Mean electroencephalographic delta activity rose by 35% in neocortex and limbic cortex against controls receiving either a cerebrospinal-fluid-like solution or any of the eight other peptides. The chemical work established a point that matters for any batch of this material: only the pure alpha-aspartyl peptide was highly active, in contrast to its beta-aspartyl isomer ^[2].

Two features of that experimental design deserve credit and one deserves caution. It was double-blind, it included the compound's own degradation fragments as controls, and it reported a specific effect rather than a general sedation. The caution is the route: intraventricular infusion places the peptide directly into the cerebral ventricles of a rabbit, bypassing every barrier a systemically administered molecule would meet, and nothing about that route supports inference to any other.

Analogues. The 2006 review notes that certain artificial structural analogues have shown slow-wave-promoting activity in rabbits — including a decapeptide structurally similar to DSIP at five of nine positions, whose optical isomer had the opposite effect ^[13]. That analogues are active while the natural occurrence of the parent remains obscure is part of what the review calls the riddle.

Findings in this section were observed in rabbits, by direct intraventricular infusion. Nothing in them establishes anything about humans.

What Is DSIP Being Researched For?

The research record is closed rather than active, and divides into three strands:

• Electroencephalographic characterisation in rabbits, 1977–1978 — the isolation, the sequence, and the double-blind comparison against fragments and analogues ^{[1, 2]}.
• Chronic insomnia in humans, 1981–1992 — four indexed controlled studies, reaching opposite conclusions ^{[3, 10, 9, 11]}.
• Withdrawal syndromes and chronic pain in humans, 1983–1998 — open and uncontrolled clinical series ^{[4, 6, 7, 12]}.

Two contemporary reviews cover the field as it stood in the mid-1980s ^{[5, 8]}, and one modern review reassesses it ^[13]. None of this is research into, or evidence about, research-grade material supplied for laboratory use.

Human Research on DSIP

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

The controlled human literature on this peptide consists of a handful of small studies conducted between 1981 and 1992. They are set out below in order, including the ones whose conclusions were negative, because the pattern across them is the finding.

Randomised report in insomnia, 1981

Design. A randomised report published as a letter in The Lancet, indexed as a clinical trial ^[3].

Result. The report is titled as a positive finding on sleep in people with insomnia. The PubMed record carries no abstract and the full text is a letter, so no population size, endpoint definition or effect size is recoverable from the indexed record, and none is stated here.

Limitations. A letter, not a full report. It is cited because it is the first randomised human result and because the later literature reacts to it, not because anything quantitative can be drawn from it.

Placebo-controlled study in severe chronic insomnia, 1987

Population. 14 middle-aged people with chronic insomnia ^[10].

Endpoint and duration. Polysomnograms at placebo baseline, at the beginning and end of treatment, and on one placebo post-treatment night; daytime psychological state and mental performance tested before and after six administrations. Placebo-controlled, double-blind, seven successive nights ^[10].

Result. The report describes substantial improvement in night sleep with the first administration and further improvement with repetition, maintained into the first post-treatment placebo night. Efficiency of night sleep and of daytime rest is described as reaching the levels of normal controls, with significant increases in daytime alertness and performance ^[10].

Limitations. Fourteen participants. No effect sizes are given in the indexed abstract, the claim of reaching "normal control" levels rests on a comparison not described in it, and the design was within-participant with placebo nights adjacent to active ones.

Double-blind crossover in chronic insomnia, 1987

Population and design. People with chronic insomnia, studied by polysomnography across four nights, 25 nmol/kg intravenously or placebo, double-blind crossover ^[9].

Result. Nocturnal awakenings, non-REM sleep latency, total waking time and waking time after sleep onset all decreased under the peptide, but none of those differences was significant against baseline or against the double-blind placebo nights. Total sleep time and non-REM sleep time increased, the increase being confined to stage 2; stage 1, slow-wave sleep and REM sleep were unchanged. Where differences against placebo were significant — non-REM sleep time and stage 2 — the same differences were already present at baseline. The authors concluded that sleep improvement under the peptide is of little clinical significance ^[9].

Limitations. Small, short, and the authors' own conclusion is the negative one. The dissociation is notable on its own terms: slow-wave sleep, the measure the compound is named after, did not change.

Double-blind parallel-group study in chronic insomnia, 1992

Population. 16 people with chronic insomnia, double-blind matched-pairs parallel-group design, five consecutive nights in the laboratory with the first for adaptation and the second for baseline ^[11].

Endpoint and duration. Sleep structure and objective and subjective sleep quality. Half received 25 nmol/kg intravenously in the afternoon before the third, fourth and fifth nights; half received a glucose solution ^[11].

Result. Objective sleep quality showed higher sleep efficiency and shorter sleep latency against placebo, and one measure of subjectively estimated tiredness fell. The authors' own analysis, however, found the significant effects weak and in part possibly attributable to an incidental change in the placebo group; no other measure changed, subjective sleep quality included. Their conclusion was that short-term treatment of chronic insomnia with this peptide is not likely to be of major therapeutic benefit ^[11].

Limitations. Sixteen participants split between two arms. The authors' interpretation of their own positive numbers is more cautious than the numbers alone would suggest, and that caution is part of the result.

Across all four, the studies describe a compound whose measurable effects on polysomnography are real but small, inconsistent between laboratories, and — in the two later and better-controlled reports — judged by the investigators themselves to be of limited clinical significance. Total participants across all four: fewer than fifty.

Preclinical Research on DSIP

Animal research

The animal literature beyond the original characterisation is thinner than the compound's reputation implies, and the contemporary reviews are the best guide to what it contained.

The 1984 review covers the isolation and characterisation achieved between 1963 and 1977 and the first reports of effects both on sleep and outside it ^[5]. The 1986 update, published only two years later, describes considerable additional literature: further sleep-inducing or sleep-supporting effects in animals, immunohistochemical and radioimmunochemical work on the natural occurrence of the peptide and the distribution of DSIP-like material in the body, and evaluation of possible therapeutic uses. Its closing assessment is the one to carry forward — that the various physiological functions of the peptide, and a possible mechanism involving modulation of adrenergic transmission, remained to be established ^[8].

That was 1986. The 2006 review, twenty years later, reports that the link between the peptide and sleep had never been further characterised, in part because of the failure to isolate the gene, the protein and any related receptor ^[13]. Two reviews, two decades apart, reaching the same verdict, is a stronger statement about this literature than any single study in it.

The tissue-distribution work is the part that aged least well. Immunoreactive material resembling the peptide proved to be distributed with high specificity in neurosecretory hypothalamic nuclei across vertebrate species — nuclei that are not particularly relevant to the function the compound was named for ^[13]. That mismatch is one of the observations that motivated the proposal that a different peptide is responsible for what has been measured.

Findings described in this section were observed in animals. Nothing in them establishes anything about humans.

Other Areas of DSIP Research

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

A second human literature exists on withdrawal syndromes, and it needs to be read with its design in view: these were open clinical series with no placebo arm and no blinding, assessed by treating clinicians.

Withdrawal syndromes, 1983. 67 people presenting with withdrawal symptoms received 25 nmol/kg intravenously as sole treatment; 49 were evaluable, and a beneficial effect was reported in 48 of them — 22 of the alcohol-withdrawal group and 26 of 27 in the opiate-withdrawal group — with immediate onset and lasting suspension of somatic symptoms and signs. Anxiety resolved more slowly, over hours. No major side effect occurred ^[4].

Withdrawal syndromes, larger series, 1984. 107 inpatients, 47 with alcohol withdrawal and 60 with opiate withdrawal, assessed by physician and nursing staff. Approximately 13% and 22% respectively did not meet the requirements for evaluation. Clinical symptoms and signs disappeared or improved markedly and rapidly in 97% of opiate and 87% of alcohol withdrawal cases. Anxiety again resolved more slowly, the course was longer for opiate withdrawal, and more administrations were required. Tolerance was described as good aside from headaches in a few participants ^[6].

The stated rationale is worth recording because it is testable and was never tested: animal work had shown that morphine, alcohol, pentobarbital and this peptide, injected into the bulbo-mesencephalo-thalamic recruiting system, all produced slow-wave sleep with numerous spindles, and that in every case the effect was reversed by naloxone — from which agonist activity at opioid receptors was postulated ^[6]. No direct receptor binding work has substantiated that postulate in the four decades since.

Response rates of 87% to 97% in an unblinded series assessed by treating staff are not evidence of efficacy. Withdrawal syndromes resolve on their own; expectancy effects in this setting are large; and no control group existed. The 1998 open trial in opioid detoxification was likewise open-label, and its PubMed record carries no abstract, so nothing quantitative is stated here from it ^[12].

Chronic pain, 1984. A pilot study in 7 people with migraine episodes and vasomotor headaches, chronic tinnitus and psychogenic pain attacks. Baseline values were compared statistically with a follow-up control period; pain levels fell significantly in 6 of the 7 after intravenous administration on five consecutive days followed by five further administrations every 48 to 72 hours, with a simultaneous significant reduction in accompanying depressive states ^[7].

Seven participants, three different pain conditions, no control group, and a before-and-after comparison. It is labelled a pilot study by its own authors and should be read as one.

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

DSIP vs Related Compounds

Structural family

None. The sequence does not correspond to any established peptide family, which is stated explicitly in the modern review of the compound ^[13]. That isolation is part of why it has no neighbouring pharmacology to draw on.

Against Semax and Selank

Semax and Selank are also short peptides with neurological research literatures, but both are rationally designed analogues of known parent sequences with identified structural logic. DSIP was isolated from an animal and its parent, if it has one, has never been found. The three are grouped together by research field, not by chemistry.

Fragments and analogues

Five metabolic fragments of the nonapeptide and two substituted analogues were tested alongside it in the original characterisation, and none reproduced its effect ^[1]. Later analogue work is described in the 2006 review ^[13]. Phosphorylated and other modified forms circulate under this name in supplier listings and are chemically distinct molecules.

Alpha- versus beta-aspartyl form

Not a related compound but a purity question specific to this peptide: the original work found the alpha-aspartyl peptide highly active and its beta-aspartyl isomer not ^[2]. Isomeric composition is therefore a meaningful analytical question here in a way it is not for most peptides.

Regulatory position

Not approved by the U.S. Food and Drug Administration for any indication, and never marketed anywhere. It holds an International Nonproprietary Name, emideltide, which reflects how far it once progressed — not an approval.

No comparison of effect between these compounds is made on this page.

Chemical & Molecular Characteristics

DSIP is an unmodified nonapeptide with free N- and C-termini. PubChem carries it as compound identifier 68816, with CAS registry number 62568-57-4 and FDA/NCATS UNII code YN28Z5YZ73. The recorded molecular formula is C35H48N10O15 and the average mass 848.8 g/mol.

Five of nine residues are glycine or alanine. Glycine appears at positions 3, 4 and 8, alanine at 2 and 6. A backbone that small and that flexible has essentially no secondary structure in solution, which is one reason no structural model of a receptor interaction has ever been proposed for it.

Strongly acidic, with no basic residue. Aspartate at position 5 and the C-terminal glutamate give two negative charges at physiological pH and there is no lysine, arginine or histidine to balance them. The peptide is therefore net negative, and its chromatographic behaviour differs markedly from the basic peptides it is usually catalogued alongside.

One tryptophan, and it is at the N-terminus. That single residue is the only strong ultraviolet chromophore in the molecule, which makes 280 nm quantification possible, and it is also the residue most vulnerable to oxidation and to photodegradation. The exposed N-terminal position compounds both.

The alpha-aspartyl form is the active one. Aspartate residues in a Asp-Ala context are prone to rearrangement through a succinimide intermediate to the beta-aspartyl isomer, and the original characterisation found that isomer inactive where the alpha form was highly active ^[2]. Mass spectrometry cannot distinguish the two — they are isomers of identical mass — so a mass-spectrometric identity check does not answer this particular question, and a purity figure by reversed-phase chromatography may or may not resolve it depending on the method.

That last point is the most practically important thing on this page about the material itself, and it is not something a molecular formula or a catalogue mass conveys.

Analytical Specifications

Analytical figures are lot-specific. Fields the catalog does not carry for the current lot are omitted rather than filled with a typical value. The certificate of analysis and the safety data sheet for the exact lot supplied are provided with a laboratory order; no purity figure on this page is a substitute for that document.

Frequently Asked Questions

Scientific References

1. Schoenenberger GA, Monnier M. Characterization of a delta-electroencephalogram (-sleep)-inducing peptide Proceedings of the National Academy of Sciences of the United States of America; 1977. PMID 265572 doi:10.1073/pnas.74.3.1282
2. Schoenenberger GA, Maier PF, Tobler HJ, et al.. The delta EEG (sleep)-inducing peptide (DSIP). XI. Amino-acid analysis, sequence, synthesis and activity of the nonapeptide Pflugers Archiv : European journal of physiology; 1978. PMID 568769
3. Schneider-Helmert D, Graf M, Schoenenberger GA. Synthetic delta-sleep-inducing peptide improves sleep in insomniacs Lancet (London, England); 1981. PMID 6112579 doi:10.1016/s0140-6736(81)92417-x
4. Dick P, Grandjean ME, Tissot R. Successful treatment of withdrawal symptoms with delta sleep-inducing peptide, a neuropeptide with potential agonistic activity on opiate receptors Neuropsychobiology; 1983. PMID 6328354 doi:10.1159/000118012
5. Graf MV, Kastin AJ. Delta-sleep-inducing peptide (DSIP): a review Neuroscience and biobehavioral reviews; 1984. PMID 6145137 doi:10.1016/0149-7634(84)90022-8
6. Dick P, Costa C, Fayolle K, et al.. DSIP in the treatment of withdrawal syndromes from alcohol and opiates European neurology; 1984. PMID 6548969 doi:10.1159/000115715
7. Larbig W, Gerber WD, Kluck M, et al.. Therapeutic effects of delta-sleep-inducing peptide (DSIP) in patients with chronic, pronounced pain episodes. A clinical pilot study European neurology; 1984. PMID 6548970 doi:10.1159/000115716
8. Graf MV, Kastin AJ. Delta-sleep-inducing peptide (DSIP): an update Peptides; 1986. PMID 3550726 doi:10.1016/0196-9781(86)90148-8
9. Monti JM, Debellis J, Alterwain P, et al.. Study of delta sleep-inducing peptide efficacy in improving sleep on short-term administration to chronic insomniacs International journal of clinical pharmacology research; 1987. PMID 3583493
10. Schneider-Helmert D. Effects of delta-sleep-inducing peptide on 24-hour sleep-wake behaviour in severe chronic insomnia European neurology; 1987. PMID 3622582 doi:10.1159/000116143
11. Bes F, Hofman W, Schuur J, et al.. Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients. A double-blind study Neuropsychobiology; 1992. PMID 1299794 doi:10.1159/000118919
12. Backmund M, Meyer K, Rothenhaeusler HB, et al.. Opioid detoxification with delta sleep-inducing peptide: results of an open clinical trial Journal of clinical psychopharmacology; 1998. PMID 9617990
13. Kovalzon VM, Strekalova TV. Delta sleep-inducing peptide (DSIP): a still unresolved riddle Journal of neurochemistry; 2006. PMID 16539679 doi:10.1111/j.1471-4159.2006.03693.x

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.

Related laboratory reagent: DSIP specifications and lot documentation