Peerless Peptides

DSIP

Delta Sleep-Inducing Peptide, synthetic Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu nonapeptide

DSIP (Delta Sleep-Inducing Peptide, FDA-assigned generic name Emideltide) is a synthetic 9-amino-acid linear peptide isolated in 1977 by Werner Schoenenberger and Marcel Monnier at the University of Basel from cerebral venous dialysate of rabbits placed in slow-wave sleep by electrical stimulation of the intralaminar thalamic area. The original cross-circulation isolation has not been independently replicated in 47 years, and no specific high-affinity DSIP receptor has been identified across that interval.

Available for laboratory research use only.

2-Day Fast Shipping

>99% Purity

Ships from Florida

USA Made & Tested

Choose your supply

Quantity

Independent Lab Results

The most comprehensive testing panel in research peptide commerce. Every batch is independently verified by ILS Laboratories — an ISO/IEC 17025 and PJLA-accredited facility in San Diego, CA.

  • Identity
  • Purity (HPLC)
  • Endotoxin (USP <85>)
  • Sterility (USP <71>)
  • Heavy metals (ICP-MS per USP <233>)
View Certificate of Analysis Program

Biochemical Profile

CAS Number
62568-57-4
Molecular Formula
C35H48N10O15
Molecular Weight
848.81 g/mol
Purity
≥99% (HPLC-UV (220 nm + 280 nm dual-wavelength). Note: Trp¹ is aromatic, so 280 nm detection is valid for DSIP, with extinction coefficient approximately 5500 M⁻¹·cm⁻¹.)
PubChem CID
68816
Amino Acid Sequence
Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu

Receptor Targets and Signaling Pathway Context

DSIP has been characterized as a 9-residue linear peptide with a Trp¹ aromatic side chain at the N-terminus and a free carboxylic acid on the C-terminal Glu⁹. Despite 47 years of investigation across European, Soviet, Russian, Indian, and Chinese laboratories, no specific high-affinity DSIP receptor has been identified in the published literature[1][2]. The 2006 Kovalzon and Strekalova review in J Neurochem framed the situation directly in its title: 'a still unresolved riddle'[3]. Twenty additional years of research have not closed that gap.

Reported binding interactions span multiple neurotransmitter systems without a single high-affinity anchor. In rodent cortical preparations, modulation of NMDA receptor signaling has been described in animal-model in vitro electrophysiology, though without the affinity and specificity characteristic of established glutamate-receptor ligands. Hippocampal and cerebellar in vitro preparations have reported GABAergic potentiation effects that are not direct GABA-A binding. Sporadic Russian reports have described α1-adrenergic and acetyltransferase modulation, with mechanism details unclear[3]. Kd values reported in the literature, where reported at all, fall in the µM range, consistent with low-affinity non-specific interactions[3].

The most concrete mechanism finding to date is indirect Met-enkephalin release. Iwata and colleagues (1989) reported that DSIP at 1 pM to 1 nM stimulated the release of immunoreactive Met-enkephalin from rat lower brainstem slices in vitro[4]. The authors framed this as an indirect opioid pathway, explicitly not direct opioid-receptor binding. No high-resolution co-crystal structure of DSIP bound to any proposed target exists in the Protein Data Bank, and no orthogonal biophysical confirmation (isothermal titration calorimetry, surface plasmon resonance, NMR) of the proposed interactions has been published by groups outside the original Basel laboratory and its post-1995 Russian successors[3].

A second structural gap parallels the receptor gap: no endogenous mammalian gene encoding DSIP has been cloned or rigorously confirmed. The UniProt entry P01158 is annotated for DSIP but is not anchored to a confirmed transcript or genomic locus in human or other mammalian sources. DSIP-like immunoreactivity has been detected in human cerebrospinal fluid, plasma, breast milk, and brain regions using antibody-based methods, but antibody-based detection is not equivalent to genomic confirmation, and the short DSIP sequence (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) renders immunological cross-reactivity structurally plausible[3]. A 2007 BLAST analysis suggested partial homology between the DSIP sequence and a putative protein from the soil bacterium Amycolatopsis coloradensis, a speculative result not subsequently pursued by structural-genomics groups[3].

Reported plasma half-life of DSIP in vitro is approximately 15 minutes, driven by aminopeptidase cleavage at the N-terminal Trp-Ala bond. This pharmacokinetic profile is structurally important for evaluating the route-asymmetry of the preclinical literature: the dosing routes used in the foundational sleep-EEG work were intraventricular or intracerebral (direct CNS delivery), not systemic, and inference from one route to the other is methodologically constrained[3].

Research Applications

EEG Slow-Wave Architecture Research

EEG slow-wave-sleep marker research is the strongest preclinical evidence base for DSIP. Across multiple animal models (rabbit, rat, mouse, cat), intraventricularly or intracerebrally injected DSIP at low picomolar to nanomolar doses has been associated with increases in slow-wave (delta-band) EEG power and changes in REM architecture[1][2]. In cats, the REM-sleep effect has been reported as more pronounced than the delta-sleep effect, complicating the 'delta sleep' naming convention[3].

Foundational papers in this domain comprise the Basel serialized 'delta EEG (sleep)-inducing peptide' research line. The 1977 PNAS isolation paper by Schoenenberger and Monnier reported the active fraction from rabbit cerebral venous dialysate as a nonapeptide producing approximately 35% increase in delta-EEG activity at the active dose in synthetic confirmation experiments, with truncated and substituted analogs producing no significant effect[1]. The 1978 Pflugers Arch full-sequencing paper (the eleventh installment in the same serialized line) confirmed the Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu sequence and synthesis route[2]. Subsequent confirmation work has come from Borbély (Zurich), Kovalzon (Moscow), Inoue (Japan), and the Schoenenberger laboratory's own continuing research through 1990.

Methodology limitation: all sleep-EEG findings sit on intraventricular or intracerebral routes (direct CNS delivery, bypassing peripheral barriers). Systemic-administration sleep-EEG effects have been smaller, less consistent, and confounded by the 15-minute plasma half-life from aminopeptidase cleavage at the N-terminal Trp-Ala bond[3].

Antinociception and Opioid-System Research

Intracerebroventricular or intracisternal DSIP administration has been associated with dose-dependent antinociceptive readouts in rodent tail-flick, hot-plate, and writhing assays. The mechanism appears not to be direct opioid-receptor binding. Iwata and colleagues (1989) reported that DSIP at 1 pM to 1 nM stimulated the release of immunoreactive Met-enkephalin from rat lower brainstem slices in vitro[4]; the authors framed this as an indirect opioid pathway routed through endogenous enkephalin release rather than direct ligand-receptor engagement.

A 1984 human pilot study from Strindberg and colleagues reported analgesic observations in chronic-pain patients (PMID 6548970) in an open-label small-N design with no placebo control[5]. No follow-up Phase 2 or Phase 3 trial has been conducted in the 40 years since publication.

The antinociception literature on DSIP sits entirely in rodent intracerebral preparations and one 1984 open-label uncontrolled human pilot. Methodology limitations applicable to the route-asymmetry critique apply: the studied route in the rodent literature is intracerebral, not systemic, and inference from one to the other is constrained by the 15-minute plasma half-life.

Withdrawal-Syndrome Research

The most-cited human pilot in the DSIP literature for withdrawal indications is the 1984 Dick, Costa, Fayolle and colleagues study in Eur Neurol[6]. The design: n=107 inpatients (47 alcohol-dependent, 60 opioid-dependent), open-label, no placebo arm, single-center, intravenous administration. The authors reported 87% symptom alleviation in alcohol-dependent patients and 97% in opioid-dependent patients.

Methodology limitations on the Dick 1984 pilot are extensive: open-label design with no placebo arm, no randomization, no blinding, no active comparator (the 1984 standard of care for opioid withdrawal included clonidine, methadone tapers, and supportive care, none directly compared). The reported 97% and 87% response rates would be implausible against a placebo arm given the natural history of monitored withdrawal in inpatient settings, and the trial does not survive the methodology standard required for a 2020s Phase 3 trial[6]. No follow-up Phase 2 or Phase 3 trial in withdrawal indications has been conducted in the 40-plus years since publication.

This 1984 open-label uncontrolled pilot is the strongest single piece of human clinical evidence in the entire DSIP literature for any withdrawal indication. If the FDA Pharmacy Compounding Advisory Committee reviews the opioid-withdrawal proposed indication on July 24, 2026 (per Federal Register doc 2026-07361), the Dick 1984 pilot will be the lead clinical citation in the docket record[7].

Stress Axis and Neuroprotection Research

DSIP has been examined in rodent preparations for effects on corticotropin levels and HPA-axis activity. The 'stress-limiting peptide' framing common in Russian-language reviews follows from these animal-model findings. No human randomized controlled trial confirmation has been published[3].

In stroke preclinical research, Tukhovskaya and colleagues (2021) reported observations on motor-function readouts in Sprague-Dawley rats after focal stroke in an animal-model study from a Russian institutional network[8]. The work sits within the broader Russian neuroprotectant program also represented by Semax and Cerebrolysin. The Western neuroprotectant Phase 3 record (NXY-059 SAINT-II, citicoline ICTUS, tirilazad RANTTAS, lubeluzole) defines a class base rate of consistent Phase 3 failure for neuroprotectant programs developed exclusively in non-Western research networks, a consideration applicable to any extrapolation from animal-model focal-stroke findings.

A distinct preclinical line examined phosphorylated DSIP (Ser⁷ phosphate, PubChem CID 172600). Roy and colleagues (2018) reported observations on spatial-memory readouts and p-CREB expression in rodents at simulated high altitude[9]. The phosphorylated variant is a structurally distinct molecule with its own preclinical literature; commercial research-grade material does not always distinguish free-acid DSIP from the phosphorylated form.

Soviet-Era Tumor and Longevity Research

A separate research line from Soviet-era Russian gerontology examined rodent lifespan and spontaneous-tumor readouts. Popovich, Voitenkov, Anisimov and collaborators reported in 2003 to 2007 Russian literature on CBA mice receiving subcutaneous DSIP: approximately 2.6× reduction in tumor incidence, 22.6% reduction in bone marrow chromosome aberrations, and 24.1% increase in maximum lifespan[10].

Anisimov is the same Khavinson-laboratory collaborator named in the Epitalon lifespan literature, and the methodology critiques applied to the Khavinson SHR mouse studies apply equally here: short-lived control colonies, single-laboratory work, no NIH Interventions Testing Program replication. No independent Western replication of any DSIP tumor-reduction or lifespan-extension finding has been published[3].

These single-laboratory Russian rodent claims do not enter modern geroscience meta-analyses; Ali and colleagues (2023, 2024) explicitly exclude Russian-arc gerontology studies for methodological reasons consistent with the broader class base rate. The findings remain unreplicated outside the originating Soviet/Russian institutional network 20-plus years after first publication[3].

Replication, Trials, and Regulatory Inflection

The 1977 cross-circulation isolation method has not been independently replicated in 47 years. No second laboratory has reported isolating DSIP from cerebral venous dialysate of hypnogenically-stimulated rabbits via the original Schoenenberger and Monnier protocol[1][2][3]. Chemical synthesis of the nonapeptide is trivially reproducible by Fmoc solid-phase peptide synthesis, and synthetic-peptide sleep-EEG effects in rabbits have been observed by multiple groups; synthetic-confirmation of activity is methodologically distinct from confirmation of the biological-isolation claim, which rests on one research group's serialized work.

Zero NCT-registered Phase 3 trials of DSIP for any indication exist on ClinicalTrials.gov; queries for 'delta sleep inducing peptide' and 'Emideltide' on the ClinicalTrials.gov v2 API return no studies as of May 2026[7]. The 1980s European pilot literature (Schneider-Helmert, Kastin, Graf and collaborators) sits in small-N (n<50), short-duration, mostly open-label or double-blind crossover designs that do not meet modern FDA Phase 2 or Phase 3 standards[11][12][13]. Multiple Swiss, German, and Italian pharmaceutical-development arcs were abandoned between 1980 and 1995 without producing an approved drug, with plausible reasons including the 15-minute plasma half-life, the unidentified mechanism, the thin replication base, and expired composition-of-matter intellectual property[3].

The DSIP regulatory present is concentrated. The FDA removed DSIP (and 11 other peptide bulk drug substances) from 503A Category 2 effective April 22, 2026; removal does not confer Category 1 status or compoundability. The FDA Pharmacy Compounding Advisory Committee has scheduled DSIP for review on July 24, 2026 (PCAC Day 2 docket), under the FDA-assigned generic name Emideltide, with the verbatim Federal Register docket text (doc 2026-07361, written-comment docket FDA-2025-N-6895, meeting-establishment docket FDA-2026-N-2979) reading: 'Emideltide (free base), Emideltide acetate' and proposed uses 'opioid withdrawal, chronic insomnia, and narcolepsy.' The Day 2 cohort places DSIP alongside Semax and Epitalon, both Russian-arc peptides[7]. DSIP was explicitly named in the October 2020 Tailor Made Compounding federal plea (Nicholasville Compounding Pharmacy, owner Joel Delk, $1.79M forfeiture); the indictment listed DSIP in the federal distribution list alongside BPC-157, Cerebrolysin, CJC-1295, Epitalon, GW-501516, Ipamorelin, LGD-4033, LL-37, Melanotan II, MK-677, PEG-MGF, Selank, and Semax[14].

Reconstitution & Storage

Recommended Diluent
Bacteriostatic water (0.9% benzyl alcohol)
Storage (lyophilized)
-20°C, dry, dark, sealed amber vials with desiccant; 18-24 months
Storage (reconstituted)
2-8°C, use within 21-28 days. Avoid freeze-thaw cycling, which accelerates Trp¹ oxidative degradation.
Shelf Life
18-24 months lyophilized

Research References

  1. [1] Schoenenberger GA, Monnier M. Characterization of a delta-electroencephalogram (-sleep)-inducing peptide. Proc Natl Acad Sci USA. 1977;74(3):1282-1286. PMID:265572
  2. [2] Schoenenberger GA, Maier PF, Tobler HJ, Wilson K, Monnier M. The delta EEG (sleep)-inducing peptide (DSIP). XI. Amino-acid analysis, sequence, synthesis and activity of the nonapeptide. Pflugers Arch. 1978;376(2):119-129. PMID:568769
  3. [3] Kovalzon VM, Strekalova TV. Delta sleep-inducing peptide (DSIP): a still unresolved riddle. J Neurochem. 2006;97(2):303-309. doi:10.1111/j.1471-4159.2006.03726.x
  4. [4] Iwata N, Kobayashi M, Sasaki T, Tanaka T, Hizukuri K, Honda K. Delta-sleep-inducing peptide (DSIP) stimulates the release of immunoreactive Met-enkephalin from rat lower brainstem slices in vitro. Brain Res. 1989;481(2):187-191. PMID:2706459
  5. [5] Strindberg L, Carlsson B, Larsson B, Markhede G, Tornquist H. Therapeutic effects of delta-sleep-inducing peptide (DSIP) in patients with chronic, pronounced pain episodes. A clinical pilot study. Acta Neurol Scand. 1984;70(6):419-425. PMID:6548970
  6. [6] Dick P, Costa C, Fayolle K, Grandjean ME, Khoshbeen A, Tissot R. DSIP in the treatment of withdrawal syndromes from alcohol and opiates. Eur Neurol. 1984;23(5):364-371. PMID:6328354
  7. [7] U.S. Food and Drug Administration. Pharmacy Compounding Advisory Committee meeting; July 23-24, 2026; establishment notice and docket. Federal Register doc 2026-07361; written-comment docket FDA-2025-N-6895; meeting-establishment docket FDA-2026-N-2979. Day 2 (July 24, 2026) docket text: 'Emideltide (free base), Emideltide acetate'; proposed uses: 'opioid withdrawal, chronic insomnia, and narcolepsy.'
  8. [8] Tukhovskaya EA, Slashcheva GA, Goryacheva NA, et al. Delta Sleep-Inducing Peptide Recovers Motor Function in SD Rats after Focal Stroke. Molecules. 2021;26(17):5173. PMID:34500605
  9. [9] Roy K, Chakrabarti A, Saha A, Khan H, Saha PK, Singh RK. Phosphorylated delta sleep inducing peptide restores spatial memory and p-CREB expression by improving sleep architecture at high altitude. Life Sci. 2018;209:282-290. PMID:30107169
  10. [10] Popovich IG, Voitenkov BO, Anisimov VN, Ivanov VT, Mikhaleva II, Zabezhinski MA, Alimova IN, Baturin DA, Zabezhinskaya VG, Yashin AI. Effect of delta-sleep inducing peptide-containing preparation Deltaran on biomarkers of aging, life span and spontaneous tumor incidence in female SHR mice. Mech Ageing Dev. 2003;124(6):721-731. PMID:12782416
  11. [11] Schneider-Helmert D, Schoenenberger GA. Effects of DSIP in man. Multifunctional psychophysiological properties besides induction of natural sleep. Experientia. 1983;39(7):680-682. PMID:6873464
  12. [12] Schneider-Helmert D. Efficacy of DSIP in middle-aged subjects with chronic insomnia. Acta Neurochir Suppl (Wien). 1986;38:97-101. PMID:3792404
  13. [13] Schneider-Helmert D, Gnirss F, Monnier M, Schenker J, Schoenenberger GA. Acute and delayed effects of DSIP (delta sleep-inducing peptide) on human sleep behavior. Int J Clin Pharmacol Ther Toxicol. 1981;19(8):341-345. PMID:7028502
  14. [14] United States Department of Justice / Food and Drug Administration Office of Criminal Investigations. Nicholasville Compounding Pharmacy (Tailor Made Compounding) and owner Joel Delk plea agreement, October 2020. U.S. District Court before Judge Gregory F. Van Tatenhove; $1.79M forfeiture. Federal distribution list explicitly named DSIP alongside BPC-157, Cerebrolysin, CJC-1295, Epitalon, GW-501516, Ipamorelin, LGD-4033, LL-37, Melanotan II, MK-677, PEG-MGF, Selank, and Semax.
  15. [15] Graf MV, Kastin AJ. Delta-sleep-inducing peptide (DSIP): an update. Peptides. 1986;7(6):1165-1187. PMID:3550726
  16. [16] Graf MV, Kastin AJ. Delta-sleep-inducing peptide (DSIP): a review. Neurosci Biobehav Rev. 1984;8(1):83-93. PMID:6145137
  17. [17] Inoue S, Honda K, Komoda Y. DSIP: a tool for investigating the sleep onset mechanism: a review. Int J Neurosci. 1988;38(3-4):407-413. PMID:3045974
  18. [18] Bjartell A, Hedner T, Hedner J. Some pharmacological effects of delta-sleep-inducing peptide (DSIP) in mice and rats. Acta Physiol Scand. 1989;135(3):395-403. PMID:2773652

Scientific Journal Author

Werner Schoenenberger, MD (originating co-investigator with Marcel Monnier, MD)

Department of Research / Department of Physiology, University of Basel

Landmark Publications

  • Schoenenberger GA, Monnier M. Characterization of a delta-electroencephalogram (-sleep)-inducing peptide. Proc Natl Acad Sci USA. 1977;74(3):1282-1286. (PMID 265572)
  • Schoenenberger GA, Maier PF, Tobler HJ, Wilson K, Monnier M. The delta EEG (sleep)-inducing peptide (DSIP). XI. Amino-acid analysis, sequence, synthesis and activity of the nonapeptide. Pflugers Arch. 1978;376(2):119-129. (PMID 568769)
  • Monnier M, Schoenenberger GA. Characterization, sequence, synthesis and specificity of a delta EEG (sleep)-inducing peptide. In: Monnier M, ed. Functions of the Nervous System. Vol 4. Elsevier; 1977.

Dr. Schoenenberger and Dr. Monnier are independently cited here as the originating researchers of DSIP at the University of Basel. There is no affiliation or commercial relationship between Dr. Schoenenberger, Dr. Monnier, the University of Basel, or any associated entity, and Peerless Peptides.

Frequently Asked Questions