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DSIP
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Delta Sleep‑Inducing Peptide, a short neuropeptide historically researched for sleep architecture and stress responses.
Key Research Properties:
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| SKU: | dsip |
|---|---|
| Purity: | >99% (HPLC Verified) |
| Form: | Lyophilized Powder |
| Storage: | Store at -20°C |
| CAS Number: | 62568-57-4 |
For Research Use Only.
All products are sold strictly for laboratory and research purposes. Products are not intended for human use or consumption of any kind.
The statements presented on this website have not been evaluated by the Food and Drug Administration (FDA). The products of this company are not intended to diagnose, treat, cure, or prevent any medical condition or disease.
All products are sold strictly for laboratory and research purposes. Products are not intended for human use or consumption of any kind.
The statements presented on this website have not been evaluated by the Food and Drug Administration (FDA). The products of this company are not intended to diagnose, treat, cure, or prevent any medical condition or disease.
What is DSIP (Delta Sleep-Inducing Peptide)?
Delta Sleep-Inducing Peptide (DSIP) is a naturally occurring nonapeptide (9 amino acids) first discovered in 1977 from the cerebral venous blood of sleeping rabbits[1]. Named for its ability to induce delta wave sleep (deep, slow-wave sleep), DSIP has been extensively studied for its sleep-promoting, stress-reducing, analgesic, and potential neuroprotective properties[2].
Sleep & Stress Regulator: DSIP is one of the earliest discovered sleep-promoting peptides, with unique properties that extend beyond simple sedation. Unlike traditional sleep medications, DSIP appears to normalize sleep architecture, reduce stress responses, and provide analgesic effects without causing dependency or tolerance in animal studies.
Biochemical Properties
- Sequence: Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu (WAGGDASGE)
- Size: 9 amino acids (~850 Da)
- Discovery: 1977 by Swiss researchers Monnier, Schoenenberger, and colleagues
- Origin: Found in brain, peripheral organs, plasma
- Half-Life: Very short (~15 minutes in circulation)
- Distribution: CNS and peripheral tissues
Primary Benefits
- Sleep Improvement: Promotes natural sleep; increases delta wave activity
- Stress Reduction: Modulates stress hormones; reduces cortisol
- Analgesic Effects: Pain reduction in chronic pain conditions
- Circadian Regulation: Helps normalize disrupted sleep-wake cycles
- Neuroprotection: Potential protective effects against oxidative stress
- Mood Regulation: May improve stress-related mood disturbances
Key Research Findings
Landmark Discoveries
- Sleep Architecture: Increases slow-wave sleep (delta sleep) without disrupting REM sleep
- Stress Hormones: Reduces stress-induced cortisol elevation; modulates HPA axis
- Pain Modulation: Analgesic effects in chronic pain patients; may potentiate opioid analgesia
- Withdrawal Symptoms: Reduces withdrawal symptoms in alcohol and opioid dependence (animal/human studies)
- Oxidative Stress: Antioxidant properties; protects against free radical damage
- Clinical Studies: Human trials in former USSR and Europe show sleep and stress benefits
DSIP vs. Traditional Sleep Aids
| Property | DSIP | Benzodiazepines/Z-Drugs |
|---|---|---|
| Mechanism | Sleep regulation; stress modulation | GABA-A receptor agonism |
| Sleep Architecture | Normalizes; increases delta sleep | Disrupts REM; reduces delta sleep |
| Tolerance | Minimal/none in animal studies | Common; requires dose escalation |
| Dependency | No evidence in studies | High risk with chronic use |
| Next-Day Effects | May improve alertness/mood | Residual sedation; cognitive impairment |
| Stress Effects | Reduces stress hormones | No stress-specific effects |
Unique Profile: DSIP's combination of sleep promotion, stress reduction, and analgesic effects—without apparent tolerance or dependency—makes it a fascinating alternative to traditional sleep medications. However, human clinical data remains limited compared to approved sleep drugs.
Mechanism of Action
DSIP's mechanism of action remains incompletely understood, but research suggests it modulates sleep-wake regulation, stress hormone systems, and pain pathways through multiple mechanisms[3].
Sleep Regulation
Delta Wave Sleep Induction
Sleep Architecture Effects: DSIP increases slow-wave sleep (Stage 3/4) without significantly disrupting REM sleep.
- Delta Wave Activity: Increases EEG delta waves (0.5-4 Hz) characteristic of deep sleep
- Sleep Latency: May reduce time to fall asleep in some studies
- Sleep Consolidation: Improves sleep continuity; reduces awakenings
- REM Preservation: Unlike many sedatives, doesn't suppress REM sleep
- Circadian Modulation: May help normalize disrupted circadian rhythms
Note: The exact receptors or pathways mediating DSIP's sleep effects remain unclear. It does not appear to act through traditional GABA or melatonin receptors.
Stress Hormone Modulation
HPA Axis Regulation
Cortisol Reduction: DSIP reduces stress-induced cortisol elevation in animal and human studies.
- HPA Axis: Modulates hypothalamic-pituitary-adrenal axis activity
- Cortisol: Reduces basal and stress-induced cortisol levels
- ACTH: May reduce ACTH secretion
- Stress Response: Blunts physiological stress responses
- Adaptogenic Effects: Helps normalize stress hormone dysregulation
Analgesic & Neuroprotective Effects
Pain Modulation & Cell Protection
Analgesic Mechanisms:
- Opioid System: May interact with endogenous opioid systems
- Pain Threshold: Increases pain threshold in animal models
- Chronic Pain: Reduces pain in chronic pain patients (clinical studies)
- Opioid Potentiation: May enhance opioid analgesia
Neuroprotective Properties:
- Antioxidant: Reduces oxidative stress; scavenges free radicals
- Cell Survival: Protects neurons from various stressors
- Lipid Peroxidation: Inhibits lipid peroxidation in brain tissue
Substance Withdrawal Effects
Addiction & Withdrawal Modulation
- Alcohol Withdrawal: Reduces withdrawal symptoms in alcoholics (clinical studies)
- Opioid Withdrawal: Alleviates withdrawal symptoms in animal models
- Stress Normalization: Helps normalize stress responses during withdrawal
- Sleep Improvement: Addresses withdrawal-induced insomnia
Mechanism Summary: DSIP's mechanisms remain partially elusive, but converging evidence suggests it acts as a sleep and stress regulator with additional analgesic and neuroprotective properties. Its lack of tolerance and dependency distinguishes it from traditional sleep medications, though more research is needed to fully elucidate its molecular targets.
Research & Evidence
DSIP has been studied since the 1970s, with extensive research in the former USSR and Europe. While some human clinical trials show promise, methodological limitations and lack of recent large-scale studies limit definitive conclusions[4].
Sleep Research
Human Sleep Studies
Historical Clinical Studies: Multiple studies from 1970s-1990s, primarily in USSR and Europe.
- Insomnia: Several studies reported improved sleep onset and quality in insomnia patients
- EEG Changes: Increased delta wave activity; improved sleep architecture
- Chronic Insomnia: Benefits observed in patients with chronic sleep disorders
- Shift Workers: May help normalize sleep in circadian rhythm disruptions
- Elderly: Some studies show sleep improvements in elderly with insomnia
Methodological Concerns: Many early studies lacked rigorous controls, blinding, or adequate sample sizes. Modern, large-scale clinical trials are needed.
Stress & HPA Axis Research
Stress Hormone Studies
- Cortisol Reduction: Multiple studies show DSIP reduces basal and stress-induced cortisol
- ACTH Suppression: Reduces ACTH in stressed animals and humans
- Stress Resilience: Animals pretreated with DSIP show reduced stress responses
- Chronic Stress: May help normalize HPA axis dysregulation in chronic stress
Pain & Addiction Research
Analgesia & Withdrawal Studies
Chronic Pain:
- Clinical Studies: Several European studies reported pain reduction in chronic pain patients
- Headache: Some benefit in chronic headache disorders
- Cancer Pain: Studied as adjunct to opioids for cancer pain
Substance Withdrawal:
- Alcoholism: Clinical studies in former USSR showed reduced withdrawal symptoms
- Opioid Dependence: Preclinical evidence for reducing withdrawal symptoms
- Sleep Normalization: Helps restore sleep during withdrawal periods
Research Status: DSIP research peaked in the 1970s-1990s, primarily in Eastern Europe. Many studies lack modern methodological rigor (placebo controls, blinding, adequate statistical power). Recent research is limited. DSIP is not approved as a drug in major markets (US, EU).
Dosing & Administration
Research Use Only: DSIP is for research purposes. No FDA approval for human use.
Research Dosing (Based on Historical Clinical Studies)
Administration Routes
Intravenous (Historical Clinical Studies):
- Clinical Doses: 25-75 mcg/kg IV (approximately 1.75-5.25 mg for 70 kg person)
- Timing: Evening administration for sleep studies
- Duration: Days to weeks in clinical studies
Subcutaneous/Intramuscular (Community Protocols):
- Conservative Dose: 100-200 mcg SC before bed
- Standard Dose: 200-500 mcg SC before bed
- Timing: 30-60 minutes before desired sleep time
- Frequency: Daily or several times per week
- Duration: Cycles of 2-4 weeks; breaks between cycles
Intranasal (Experimental):
- Dose: Variable; some community protocols use 100-300 mcg intranasal
- Advantage: Non-invasive; may improve bioavailability vs. oral
- Limitation: Limited data on intranasal DSIP
Bioavailability Challenge: DSIP has very short half-life (~15 min) and poor oral bioavailability. Parenteral or intranasal routes are necessary for activity. Dosing protocols are largely speculative based on old clinical studies and community reports.
Reconstitution & Storage
- Lyophilized Powder: Store at -20°C until reconstitution
- Reconstitution: Bacteriostatic water for injection
- Reconstituted Storage: Refrigerate at 2-8°C; use within 5-7 days (short peptide stability)
- Handling: Gently swirl; avoid vigorous shaking; protect from light
Safety & Side Effects
Historical clinical studies reported minimal adverse effects, though systematic modern safety data is lacking[5].
Historical Safety Profile
Clinical Studies (1970s-1990s): Generally reported good tolerability with minimal side effects.
Common Observations:
- Well-Tolerated: Most studies reported minimal adverse events
- No Dependency: No evidence of tolerance or physical dependence in studies
- No Next-Day Sedation: Unlike benzodiazepines, minimal residual sedation reported
- Injection Site Reactions: Mild discomfort with SC/IM injections (as expected)
Rare/Occasional Effects:
- Vivid Dreams: Some reports of more vivid or intense dreams
- Morning Fatigue: Occasional reports of morning grogginess (infrequent)
- Headache: Rare reports of mild headache
Limited Modern Data: Comprehensive modern safety studies are lacking. Historical studies had limited systematic adverse event reporting. Long-term safety (>months) is not well-characterized. Community use is experimental.
Contraindications & Cautions: Given limited data, individuals with serious medical conditions, pregnant/nursing women, and those on multiple medications should avoid use. Not recommended for self-administration without medical oversight.
Frequently Asked Questions
DSIP differs fundamentally: Melatonin is a circadian signal that promotes sleep onset but doesn't directly induce sleep. Benzodiazepines/Z-drugs cause sedation but disrupt natural sleep architecture and cause tolerance/dependency. DSIP appears to normalize sleep architecture, increase deep sleep, and reduce stress—without tolerance in animal studies. However, DSIP has much less clinical validation than these alternatives.
Animal studies and limited human data suggest DSIP does not cause tolerance (need for increasing doses) or physical dependence. This is a major theoretical advantage over benzodiazepines. However, long-term human safety data is limited, so definitive statements cannot be made.
Several factors: (1) Most research was in the USSR/Eastern Europe with limited Western validation, (2) Short half-life (~15 min) makes it impractical for oral formulation, (3) Lack of commercial development and modern Phase 3 trials, (4) Unclear mechanism and receptor targets hindered drug development, (5) Competition from established sleep medications. DSIP remains a research peptide without regulatory approval.
Oral bioavailability of DSIP is extremely poor due to rapid peptide degradation in the GI tract. Clinical studies used IV administration. Community protocols typically use subcutaneous or intranasal routes. Oral DSIP is unlikely to be effective without special formulation strategies (e.g., peptide analogs, delivery systems).
No. DSIP is not FDA-approved for any indication. It has not undergone modern Phase 3 clinical trials. Available for research purposes only. Despite decades of research, it remains an investigational peptide without regulatory approval in major markets.
Historical studies generally reported minimal next-day effects, with some even noting improved daytime alertness and mood. This contrasts with benzodiazepines, which commonly cause residual sedation. However, individual responses vary, and systematic studies of next-day cognitive/motor function are limited.
Clinical Trials & Research Status
Delta Sleep-Inducing Peptide (DSIP) research was most active from the 1970s through 1990s, primarily in Europe (Switzerland, Austria, Germany) and the USSR. Clinical trials were conducted but predate modern registration systems like ClinicalTrials.gov[1][2].
Historical Research Context: Most DSIP clinical studies were conducted before 1990 and predate modern trial registration requirements (ClinicalTrials.gov established 2000). Many studies appeared in European journals with varying methodological rigor. The peptide has NOT been approved by FDA or any regulatory agency. DSIP remains a research chemical with incomplete modern clinical validation.
Published Clinical Trial
A Clinical Trial with DSIP (1984)
Publication: European Neurology, 1984;23(5):386
Link: Karger.com: A Clinical Trial with DSIP
Study Type: Clinical trial published in peer-reviewed European neurology journal
Era: Early 1980s - conducted during peak DSIP research period
Historical Context: This represents one of the formal clinical trials conducted on DSIP during its active research period in Europe. Full trial details, methodology, and results would require accessing the complete publication. Most DSIP trials from this era had smaller sample sizes and different standards than modern FDA Phase 2/3 protocols.
Historical Sleep Research
Insomnia & Sleep Quality Studies (1970s-1990s)
Research Era: Multiple studies from 1970s-1990s in Switzerland, Austria, Germany, and USSR examined DSIP's effects on sleep[3][8].
Key Research Areas:
- Sleep Induction: Studies examined DSIP's ability to promote delta (slow-wave) sleep in insomnia patients
- EEG Monitoring: Polysomnography documented changes in sleep architecture and delta wave activity
- Circadian Effects: Research on shift workers and jet lag investigated sleep pattern normalization
- Stress-Related Sleep Disorders: Studies in patients with anxiety-related insomnia
Methodological Limitations: Many historical studies lacked rigorous placebo controls, double-blinding, or adequate sample sizes by modern standards. Results require replication in contemporary Phase 2/3 clinical trials.
Why No Modern Trials?
Barriers to Clinical Development
Despite initial promise, DSIP has not progressed to modern Phase 3 trials due to several challenges[2][6]:
- Pharmacokinetics: Very short half-life (~15 minutes) makes clinical use impractical; requires frequent dosing or continuous infusion[9]
- Blood-Brain Barrier: Permeability studies show limited but variable BBB crossing, complicating CNS delivery[4][7]
- Mechanism Uncertainty: Molecular targets and receptor(s) remain unidentified despite decades of research[2]
- Formulation Challenges: Requires parenteral administration; no convenient oral formulation developed
- Commercial Viability: Generic nonapeptide; difficult to patent; limited pharmaceutical industry interest
- Regulatory Path: Would require expensive modern Phase 2/3 trials ($50M+) without clear ROI
- Degradation: Subject to rapid enzymatic degradation in plasma and serum[11]
Find More Research: Search PubMed for DSIP | Google Scholar
Critical Status Summary: DSIP has an extensive but dated research history (1970s-1990s) suggesting potential sleep and stress benefits. However, the lack of modern, rigorously conducted Phase 3 clinical trials means its efficacy and safety remain incompletely validated by contemporary FDA standards. DSIP is NOT approved for any medical use and remains a research chemical. The peptide faces significant pharmacokinetic, mechanistic, and commercial barriers to clinical development.
References & Scientific Citations
Research Integrity:
All references are verified publications from peer-reviewed journals with direct links to sources. DSIP research spans from the 1970s discovery through modern investigations.
- Graf MV, Kastin AJ. Delta-sleep-inducing peptide (DSIP): a review. Neuroscience & Biobehavioral Reviews. 1984;8(1):83-93. [ScienceDirect] - Cited by 126 - Comprehensive review article
- Kovalzon VM, Strekalova TV. Delta sleep‐inducing peptide (DSIP): a still unresolved riddle. Journal of Neurochemistry. 2006;97(2):303-309. [Wiley] - Cited by 29 - Modern critical review
- Kastin AJ, Banks WA, Castellanos PF, Nissen C. Differential penetration of DSIP peptides into rat brain. Pharmacology Biochemistry and Behavior. 1982;17(5):1187-1191. [ScienceDirect] - Cited by 49
- Kastin AJ, Nissen C, Coy DH. Permeability of blood-brain barrier to DSIP peptides. Pharmacology Biochemistry and Behavior. 1981;15(6):955-959. [ScienceDirect] - Cited by 65 - BBB permeability study
- Gray RA, Vander Velde DG, Burke CJ, Manning MC. Delta-sleep-inducing peptide: solution conformational studies of a membrane-permeable peptide. Biochemistry. 1994;33(6):1323-1331. [ACS Publications] - Cited by 84 - Structural analysis
- Graf MV, Kastin AJ. Delta-sleep-inducing peptide (DSIP): an update. Peptides. 1986;7(6):1165-1187. [ScienceDirect] - Cited by 173 - Comprehensive update review
- Zlokovic BV, Segal MB, Davson H, Jankov RM. Passage of delta sleep-inducing peptide (DSIP) across the blood-cerebrospinal fluid barrier. Peptides. 1988;9(2):309-315. [ScienceDirect] - Cited by 32 - CSF barrier transport study
- Kastin AJ, Olson GA, Schally AV, Coy DH. DSIP—more than a sleep peptide? Trends in Neurosciences. 1980;3(7):163-165. [Cell Press] - Cited by 52 - Early perspectives
- Khvatova EM, Samartzev VN, Zagoskin PP, et al. Delta sleep inducing peptide (DSIP): effect on respiration activity in rat brain mitochondria and stress protective potency under experimental hypoxia. Peptides. 2003;24(2):307-311. [ScienceDirect] - Cited by 59 - Mitochondrial effects
- Pollard BJ, Pomfrett CJD. Delta sleep-inducing peptide. European Journal of Anaesthesiology. 2001;18(7):419-426. [Cambridge] - Cited by 36 - Clinical review
- Graf MV, Saegesser B, Schoenenberger GA. Degradation and aggregation of delta sleep-inducing peptide (DSIP) and two analogs in plasma and serum. Peptides. 1987;8(2):397-402. [ScienceDirect] - Cited by 10 - Stability/degradation study
- Banks WA, Kastin AJ, Coy DH, Angulo E. Entry of DSIP peptides into dog CSF: Role of physicochemical and pharmacokinetic parameters. Brain Research Bulletin. 1986;16(5):765-771. [ScienceDirect] - Cited by 51 - CSF entry pharmacokinetics
- Mu X, Qu L, Yin L, Wang L, Liu X, Liu D. Pichia pastoris secreted peptides crossing the blood-brain barrier and DSIP fusion peptide efficacy in PCPA-induced insomnia mouse models. Frontiers in Pharmacology. 2024;15:1439536. [Frontiers] - Cited by 1 - Recent 2024 research on BBB delivery
Disclaimer:
ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE ARE FOR INFORMATIONAL AND EDUCATIONAL PURPOSES ONLY. The products offered are for in-vitro laboratory research use only. These products are not medicines or drugs and have not been approved by the FDA to prevent, treat, or cure any medical condition, ailment, or disease. DSIP is NOT approved for human use. All research cited is from historical and preclinical studies only.
Additional Research: Search PubMed for DSIP | Google Scholar for DSIP Research
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