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  1. #1
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    Delta sleep-inducing peptide

    Found across this recently, its a pretty interesting compound and was wondering if anyone can comment on it. Theres studies on pubmed but not many, full write up on wikipedia.

    Discovery

    Delta sleep-inducing peptide, abbreviated DSIP, was first discovered in 1974 by the Swiss Schoenenberger-Monnier group who isolated it from the cerebral venous blood of rabbits in an induced state of sleep. It was primarily believed to be involved in sleep regulation due to its apparent ability to induce slow-wave sleep in rabbits, but studies on the subject have been contradictory.[1]
    [edit] Structure and Interactions

    DSIP is an amphiphilic peptide of molecular weight 850 daltons with the amino acid motif:
    N-Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu-C[2]

    It has been found in both free and bound forms in the hypothalamus, limbic system and pituitary as well as various peripheral organs, tissues and body fluids.[3] In the pituitary it co-localises with many peptide and non-peptide mediators such as corticotropin-like intermediate peptide (CLIP), adrenocorticotrophic hormone (ACTH), melanocyte-stimulating hormone (MSH), thyroid-stimulating hormone (TSH) and melanin concentrating hormone (MCH). It is abundant in the gut secretory cells and in the pancreas where it co-localises with glucagon.[4]

    In the brain its action may be mediated by NMDA receptors.[5]

    It is unknown where DSIP is synthesized.

    In vitro it has been found to have a low molecular stability with a half life of only 15 minutes due to the action of a specific aminopeptidase-like enzyme.[6] It has been suggested that in the body it complexes with carrier proteins to prevent degradation, or exists as a component of a large precursor molecule,[7] but as yet no structure or gene has been found for this precursor.

    Evidence supports the current belief that it is regulated by glucocorticoids.[8]

    Gimble et al. suggest that DSIP interacts with components of the MAPK cascade and is homologous to glucocorticoid-induced leucine zipper (GILZ).[9] GILZ can be induced by Dexamethasone. It prevents Raf-1 activation, which inhibits phosphorylation and activation of ERK. See [1] for image showing the pathway analysis of DSIP [10]
    [edit] Function

    Many roles for DSIP have been suggested following research carried out using peptide analogues with a greater molecular stability [11] and through measuring DSIP-like immunological (DSIP-LI) response by injecting DSIP antiserum and antibodies.[12]
    [edit] Roles in endocrine regulation

    * Decreases basal corticotropin level and blocks its release.[13]
    * Stimulates release of luteinizing hormone (LH).[14]
    * Stimulates release of somatoliberin and somatotrophin secretion and inhibits somatostatin secretion.[15]

    [edit] Roles in physiological processes

    * Can act as a stress limiting factor.[16][17][18]
    * May have a direct or indirect effect on body temperature and alleviating hypothermia.[19][20][21]
    * Can normalize blood pressure and myocardial contraction.[22].[23]
    * It has been shown to enhance the efficiency of oxidative phosphorylation in rat mitochondria in vitro, suggesting it may have antioxidant effects.[24]
    * There is also conflicting evidence as to its involvement in sleep patterns. Some studies suggest a link between DSIP and slow-wave sleep (SWS) promotion[25][26] and suppression of paradoxical sleep, (PS)[27][28] while some studies show no correlation.[29] Stronger effects on sleep have been noted for the synthesized analogues of DSIP.[30]
    * It may have an impact on human lens epithelial cell function via the MAPK pathway, which is involved in cell proliferation, differentiation, motility, survival, and apoptosis.[31]

    [edit] Roles in Disease and Medicine

    * It has been found to have anticarcinogenic properties. In a study on mice, injecting a preparation of DSIP over the mice’s lifetime decreased total spontaneous tumor incidence 2.6-fold.[32]

    * The same study found it to also have geroprotective effects: it slowed down the age-related switching-off of oestrous function; it decreased by 22.6% the frequency of chromosome aberrations in bone marrow cells and it increased by 24.1% maximum life span in comparison with the control group.

    * Levels of DSIP may be significant in patients diagnosed with major depressive disorder (MDD). In several studies, levels of DSIP in the plasma and cerebrospinal fluid are significantly deviated from the norm in patients with MDD, though there are contradictions as to whether levels are higher or lower than healthy control patients.[33][34][35]

    * Studies have demonstrated a direct link between GILZ expression (homologous to DSIP) and adipogenesis which has links to obesity and metabolic syndrome.[36]

    * In studies on rats with metaphit-induced epilepsy DSIP acted as an anticonvulsant, significantly decreasing the incidence and duration of fits suggesting DSIP as a potential treatment for epilepsy.[37][38]

    * DSIP has been found to have an analgesic effect. In studies on mice it was found to have a potent antinociceptive effect when administered intracerebroventricularly or intracisternally (see: Route of administration).[39]

    * Due to its possible effects on sleep and nociception, trials have been carried out to determine whether DSIP can be used as an anaesthetic. One such study found that administration of DSIP to humans as an adjunct to isoflurane anaesthesia actually increased the heart rate and reduced the depth of anaesthesia instead of deepening it as expected.[40]

    * Low plasma concentrations of DSIP have been found in patients with Cushing's syndrome.[41]

    * In Alzheimer’s patients levels of DSIP have been found to be slightly elevated, though this is unlikely to be causal.[42]

    * A preparation of DSIP, Deltaran, has been used to correct central nervous system function in children after antiblastomic therapy. Ten children aged 3–16 years were given a ten-day course of Deltaran and their bioelectric activity recorded. It was found that the chemotherapy-induced impairment in the bioelectrical activity of 9 out of the 10 children was reduced by administration of DSIP.[43]

    * DSIP can act antagonistically on opiate receptors to significantly inhibit the development of opioid and alcohol dependence and is currently being used in clinical trials to treat withdrawal syndrome.[44][45] In one such trial it was reported that in 97% of opiate-dependent and 87% of alcohol-dependent patients the symptoms were alleviated by DSIP administration.[46]

    * Studies have shown that administration of DSIP can alleviate narcolepsy and normalize disturbed sleeping patterns.[47][48]
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  2. #2
    Registered User Mike83's Avatar
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    References

    1. ^ Schoenenberger GA, Maier PF, Tobler HJ and Monnier M (1977). "A naturally occurring delta-EEG enhancing nonapeptide in rabbits". European Journal of Physiology 369: 99–109.
    2. ^ Kovalzon VM and Strekalova TV (2006). "Delta sleep-inducing peptide (DSIP): a still unresolved riddle". Journal of Neurochemistry 97: 303–309.
    3. ^ Charnay Y, Bouras C, Vallet PG, Golaz J, Guntern R, Constantinidis J (1989). "Immunohistochemical distribution of delta sleep inducing peptide in the rabbit brain and hypophysis". Neuroendocrinology 49: 169–175.
    4. ^ Kovalzon VM and Strekalova TV (2006). "Delta sleep-inducing peptide (DSIP): a still unresolved riddle". Journal of Neurochemistry 97: 303–309.
    5. ^ Sudakova KV, Umriukhina PE, Rayevskyb KS (2004). "Delta-sleep inducing peptide and neuronal activity after glutamate microiontophoresis: the role of NMDA-receptors". Pathophysiology 11: 81–86.
    6. ^ Schoenenberger GA (1984). "Characterization, properties and multivariate functions of Delta-Sleep Inducing Peptide (DSIP)". European Neurology 23: 321–345.
    7. ^ Endogenous sleep substances and sleep regulation. Tokyo and BV, Utrecht, Netherlands: Japan scientific societies press, VNU science press. 1985.
    8. ^ Westrin A, Ekman R, and Traskman-Bendz L (1998). "High Delta Sleep-Inducing Peptide-Like Immunoreactivity in Plasma in Suicidal Patients with Major Depressive Disorder". Biological Psychiatry 43: 734–739.
    9. ^ Gimble JM, Ptitsyn AA, Goh BC, Hebert T, Yu G, Wu X, Zvonic S, Shi X-M and Floyd ZE (2009). "Delta sleep-inducing peptide and glucocorticoidinduced leucine zipper: potential links between circadian mechanisms and obesity?". Obesity reviews 10: 46–51.
    10. ^ © The Association for Research in Vision and Ophthalmology, Inc. (2007) http://www.iovs.org/cgi/content/full/48/4/1724/F4 retrieved: 17/11/09
    11. ^ synthesized by V. N. Kalikhevich and S. I. Churkina, University Chemical Institute, St. Petersburg, Russia, and I. I. Mikhaleva and I. A. Prudchenko, Institute of Bio-organic Chemistry, Russian Academy of Sciences, Moscow
    12. ^ Charnay Y, Golaz J, Vallet PG, Bouras C (1992). "Production and immunohistochemical application of monoclonal antibodies against delta sleep-inducing peptide". J Chem Neuroanat 5: 503–9.
    13. ^ Schoenenberger GA (1984). "Characterization, properties and multivariate functions of Delta-Sleep Inducing Peptide (DSIP)". European Neurology 23: 321–345.
    14. ^ Iyer KS and McCann SM (1987). "Delta sleep inducing peptide (DSIP) stimulates the release of LH but not FSH via a hypothalamic site of action in the rat". Brain Research Bulletin 15: 535–538.
    15. ^ Kovalzon VM (1994). "DSIP: a sleep peptide or unknown hypothalamic hormone?". J. Evol. Biochem. Physiol. 30: 195–199.
    16. ^ Stress: Neuroendocrine and Molecular Approaches. Amsterdam: Gordon and Breach Science Publishers. 1992. pp. p59-72.
    17. ^ Sudakova KV, Coghlan JP, Kotov AV, Salieva RM, Polyntsev YV, Koplik EV (1995). "Delta-sleep inducing peptide sequels in mechanisms of resistance to emotional stress". Ann. N.Y. Acad. Sci. 771: 240–251.
    18. ^ Khvatova EM, Samartzev VN, Zagoskin PP, Prudchenko IA, Mikhaleva II (2003). "Delta sleep inducing peptide (DSIP): effect on respiration activity in rat brain mitochondria and stress protective potency under experimental hypoxia". Peptides 24: 307–311.
    19. ^ Pollard BJ and Pomfrett CJD (2001). "Delta sleep-inducing peptide". Eur. J. Anaesthesiol. 18: 419–422.
    20. ^ Yehuda S, Kastin AJ and Coy DH (1980). "Thermoragulatory and locomotor effects of DSIP: paradoxical interaction with d-amphetamine". Pharmacol. Biochem. Behav. 13: 895–900.
    21. ^ Yehuda S and Mostofsky DI (1984). "Modification of the hypothermic circadian cycles induced by DSIP and melatonin in pinealectomized and hypophysectomised rats". Peptides 5: 495–497.
    22. ^ Schoenenberger GA (1984). "Characterization, properties and multivariate functions of Delta-Sleep Inducing Peptide (DSIP)". European Neurology 23: 321–345.
    23. ^ Yehuda S and Carasso R (1988). "DSIP – a tool for investigating the sleep onset mechanism: a review". International J. Neurosci. 38: 345–353.
    24. ^ Khvatova EM, Samartzev VN, Zagoskin PP, Prudchenko IA, Mikhaleva II (2003). "Delta sleep inducing peptide (DSIP): effect on respiration activity in rat brain mitochondria and stress protective potency under experimental hypoxia". Peptides 24: 307–311.
    25. ^ Iyer KS, Marks GA, Kastin AJ, and McCann SM (1988). "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 U S A 85: 3653–3656.
    26. ^ Susić V, Masirević G, Totić S (1987). "The effects of delta-sleep-inducing peptide (DSIP) on wakefulness and sleep patterns in the cat". Brain Research 414: 262–70.
    27. ^ Seifritz E, Muller M, Schonenberger G, Trachsel L, Hemmeter U, Hatzinger M, Ernst A, Moore P and Holsboer-Trachsler E (1995). "Human plasma DSIP decreases at the initiation of sleep at different circadian times". Peptides 16: 1475–1481.
    28. ^ Steiger A and Holsboer F (1997). "Neuropeptides and human sleep". Sleep 20: 1038–1052.
    29. ^ Nakagaki K, Ebihara S, Usui S, Honda Y, Takahashi Y, Kato N (1986). "Effects of intraventricular injection of anti-DSIP serum on sleep in rats". Yakubutsu Seishin Kodo (Japanese journal of psychopharmacology) 6: 259–65.
    30. ^ Kovalzon VM (2001). "Sleep-Inducing Properties of DSIP Analogs: Structural and Functional Relationships". Biology Bulletin 28: 394–400.
    31. ^ Gupta V, Awasthi N and Wagner BJ (2007). "Specific Activation of the Glucocorticoid Receptor and Modulation of Signal Transduction Pathways in Human Lens Epithelial Cells". Investigative Ophthalmology and Visual Science 48: 1724–1734.
    32. ^ Popovich IG, Voitenkov BO, Anisimov VN, Ivanov VT, Mikhaleva II, Zabezhinski MA, Alimova IN, Baturin DA, Zavarzina NY, Rosenfeld SV, Semenchenko AV, Yashin AI (2003). "Effect of delta-sleep inducing peptide-containing preparation Deltaran on biomarkers of aging, life span and spontaneous tumor incidence in female SHR mice". Mechanisms of Ageing and Development 124: 721–731.
    33. ^ Westrin A, Ekman R, and Traskman-Bendz L (1998). "High Delta Sleep-Inducing Peptide-Like Immunoreactivity in Plasma in Suicidal Patients with Major Depressive Disorder". Biological Psychiatry 43: 734–739.
    34. ^ Walleus H, Widerlöv E and Ekman R (1985). "Decreased concentrations of delta-sleep inducing peptide in plasma and cerebrospinal fluid from depressed patients". Nordic Journal of Psychiatry 39: 63–67.
    35. ^ Bjartell A, Ekman R, Sundler F and Widerlöv E (1988). "Delta sleep-inducing peptide (DSIP): An overview of central actions and possible relationship to psychiatric illnesses". Nordic Journal of Psychiatry 42: 111–117.
    36. ^ Shi X, Shi W, Li Q, Song B, Wan M, Bai S (2003). "A glucocorticoid-induced leucine-zipper protein, GILZ, inhibits adipogenesis of mesenchymal cells". EMBO Rep 4: 374–380.
    37. ^ Stanojilovic OP, Zivanovic DP and Su Sic VT (2002). "The effects of Delta Sleep-Inducing Peptide on incidence and severity in metaphit-induced epilepsy in rats". Pharmacological Research 45: 241–247.
    38. ^ Stanojlovic OP, Zivanovic DP, Mirkovic S, Mikhaleva II (2004). "Delta sleep-inducing peptide and its tetrapeptide analogue alleviate severity of metaphit seizures". Pharmacology, Biochemistry and Behavior 77: 227–234.
    39. ^ Nakamura A, Nakashima M, Sugao T, Kanemoto H, Fukumura Y, Shiomi H (1988). "Potent antinociceptive effect of centrally administered delta-sleep-inducing peptide (DSIP)". Eur J Pharmacol 155: 247–53.
    40. ^ Pomfrett CJD, Dolling S, Anders NRK, Glover DG, Bryan A, Pollard BJ (2009). "Delta sleep-inducing peptide alters bispectral index, the electroencephalogram and heart rate variability when used as an adjunct to isoflurane anaesthesia". Eur J Anaesthesiol 26: 128–34.
    41. ^ Friedman TC, García-Borreguero D, Hardwick D, Akuete CN, Doppman JL, Dorn LD, Barker CN, Yanovski JA, Chrousos GP (1994). "Decreased Delta-Sleep and Plasma Delta-Sleep-Inducing Peptide in Patients with Cushing Syndrome". Clinical Neuroendocrinology 60: 626–634.
    42. ^ Torreilles F and Touchon J (2002). "Pathogenic theories and intrathecal analysis of the sporadic form of Alzheimer’s disease". Progress in Neurobiology 66: 191–203.
    43. ^ Sinyukhin AB, Timoshinov GP, Komilov VA, Shabanov PD (2009). "Delta sleep-inducing peptide analogue corrects the eNS functional state of children treated with antiblastomic therapy". European Neuropsychopharmacology 19: S681.
    44. ^ Soyka M and Rothenhaeusler H (1997). "Delta Sleep-Inducing Peptide Opioid Detoxification". Am. J. Psychiat. 154: 714–715.
    45. ^ Yukhananov RY, Tennila TML, Miroshnichenko II, Kudrina VS, Ushakov AN and Melnik EI (1992). "Ethanol and Delta Sleep Inducing Peptide effects on brain monoamines". Pharmacol. Bio-chem. Behav. 43: 683–687.
    46. ^ Backmund M, Meyer K, Rothenhaeusler HB and Soyka M (1998). "Opioid detoxification with delta sleep-inducing peptide: results of an open clinical trial.". J. Clin. Psychopharmacol. 18: 257–258.
    47. ^ Schneider-Helmert D (1986). "DSIP in Sleep Disturbances". Eur Neurol 25: 154–157.
    48. ^ Schneider-Helmert D and Schoenenberger GA (1981). "The influence of synthetic DSIP (delta-sleep-inducing-peptide) on disturbed human sleep". Cellular and Molecular Life Sciences 37: 913–917.
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  3. #3
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    Not sure theres any practical application of this to working out, though insomniacs have experimented with it to great success.
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    Originally Posted by De__eB View Post
    Not sure theres any practical application of this to working out, though insomniacs have experimented with it to great success.
    I have been testing this through a lab rat and it works amazing!!!!!!! I believe there is a massive gh output through some channels. Body comp changing amazing fast and sleeping better than ever.
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    Originally Posted by Mike83 View Post
    I have been testing this through a lab rat and it works amazing!!!!!!! I believe there is a massive gh output through some channels. Body comp changing amazing fast and sleeping better than ever.
    Is administration IV?
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  6. #6
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    Originally Posted by Robboe View Post
    Is administration IV?
    yes through a lap tech with experience.
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    Can anyone with any knowledge on this chime in? Theres very little information out there on it. Some pubmed studies but not much information in general.
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    Originally Posted by Mike83 View Post
    Can anyone with any knowledge on this chime in? Theres very little information out there on it. Some pubmed studies but not much information in general.
    Just curious as to what kind of information you are looking for. Anything specific?
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    Delta Sleep Inducing Peptide (DSIP) (5 vials)

    Item #: DSIP 5mg (5 vials)
    Delta sleep-inducing peptide, abbreviated DSIP, was first discovered in 1974 by the Swiss Schoenenberger-Monnier group who isolated it from the cerebral venous blood of rabbits in an induced state of sleep. It was primarily believed to be involved in sleep regulation due to its apparent ability to induce slow-wave sleep.

    •Decreases basal corticotropin level and blocks its release.
    •Stimulates release of luteinizing hormone.
    •Stimulates release of somatoliberin and somatotrophin secretion and inhibits somatostatin secretion.
    Roles in physiological processes:
    •Can act as a stress limiting factor.
    •May have a direct or indirect effect on body temperature and alleviating hypothermia.
    •Can normalize blood pressure and myocardial contraction.
    •It has been shown to enhance the efficiency of oxidative phosphorylation in rat mitochondria in vitro, suggesting it may have antioxidant effects.

    There is also conflicting evidence as to its involvement in sleep patterns. Some studies suggest a link between DSIP and slow-wave sleep (SWS) promotion. It has been found to have anticarcinogenic properties. In a study on mice, injecting a preparation of DSIP over the mice’s lifetime decreased total spontaneous tumor incidence 2.6-fold. The same study found it to also have geroprotective effects: it slowed down the age-related switching-off of oestrous function; it decreased by 22.6% the frequency of chromosome aberrations in bone marrow cells and it increased by 24.1% maximum life span in comparison with the control group.

    Levels of DSIP may be significant in patients diagnosed with major depressive disorder (MDD). In several studies, levels of DSIP in the plasma and cerebrospinal fluid are significantly deviated from the norm in patients with MDD, though there are contradictions as to whether levels are higher or lower than healthy control patients. Studies have shown that administration of DSIP can alleviate narcolepsy and normalize disturbed sleeping patterns.
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    Originally Posted by NO HYPE View Post
    Just curious as to what kind of information you are looking for. Anything specific?
    gh responses to humans, negative effects, positives, pm sent.
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    European Journal of Anaesthesiology:
    July 2001 - Volume 18 - Issue 7 - pp 419-422
    Delta sleep-inducing peptide
    Pollard, B. J.; Pomfrett, C. J. D.

    Delta sleep-inducing peptide (DSIP) is a naturally occurring substance, which was originally isolated from rabbit brain in 1977 [1]. This curious substance is a nonapeptide that is normally synthesized in the hypothalamus and targets multiple sites including some within the brainstem [2]. As its name suggests DSIP promotes sleep and this has been demonstrated in rabbits, mice, rats, cats and human beings [3-5]. In fact DSIP promotes a particular type of sleep which is characterized by an increase in the delta rhythm of the EEG.

    DSIP is normally present in minute amounts in the blood. Brain and plasma DSIP concentrations exhibit a marked diurnal variation [6] and there has been shown to be a correlation between DSIP plasma concentrations and circadian rhythm in human beings. Concentrations are low in the mornings and higher in the afternoons. An elevation of endogenous DSIP concentration has been shown to be associated with suppression of both slow-wave sleep and rapid-eye-movement sleep and interestingly also with body temperature [7]. Plasma concentrations of DSIP are influenced by the initiation of sleep [8]. Patients with Cushing's syndrome suffer from a lack of slow-wave sleep but the diurnal variation in slow-wave and rapid-eye-movement sleep in those patients appears to be similar to that in normal patients [9].

    When compared with most other peptides, DSIP is unusual in that it can freely cross the blood-brain barrier and is readily absorbed from the gut without being denatured by enzymes [10,11]. DSIP is present in relatively high concentrations in human milk (10-30 ng mL-1). Any mother who has breast-fed her babies will attest to the ability of a feed to induce sleep. However, a feed of artificial milk may have a similar effect, and it is not known whether DSIP concentrations are related to the sleep-wake cycle in human neonates [12].

    DSIP has been synthesized. Administration of the synthetic substance does not induce tolerance [13]. DSIP can be assayed by several techniques including radioimmunoassay (RIA), enzyme immunoassay and high-performance liquid chromatography with RIA [14-16]. DSIP has a half-life in human plasma of between 7 and 8 min [2]. It is degraded in blood, the pathway involving the amino-peptidases [17]. A potential drug interaction might therefore be envisaged between DSIP and drugs which inhibit or are themselves metabolized by peptidases. Captopril is one such agent and patients currently undergoing treatment with any of the angiotensin-converting enzyme inhibitors should probably be excluded from any DSIP treatment protocol until further studies have been undertaken.

    DSIP and sleep
    The innate controlling mechanisms of sleep have fascinated scientists for generations and many different endogenous compounds have been proposed as controllers of sleep over the years. These include cholecystokinin, prostaglandin I2 and various unknown substances labelled 'sleep-promoting substances'. Indeed, the majority of humoral mediators seem to have some relation to sleep by, for example, affecting circadian rhythms or arousal states. In some cases, however, it is not clear if the humoral mediator is driving the sleep pattern or responding to the sleep pattern.

    Since the discovery of DSIP a number of studies have been undertaken to test the hypothesis that DSIP may be the principal endogenous sleep factor. It is reported to increase the 'pressure to sleep' in human subjects who have been injected with small doses and this, together with its ability to induce delta-wave sleep, led to its consideration as a treatment for insomnia. A number of studies have examined this use with varied success [18-21].

    DSIP has been described as a sleep-promoting substance rather than a sedative. There is a modulating effect on sleep and wake functions with a greater activity in circumstances where sleep is disturbed. There are minimal effects in healthy subjects who are not suffering from sleep disturbance [22]. DSIP is not a night sedation drug which needs to be given just before retiring. A dose of DSIP given during the course of the day will promote improved sleep on the next night and for several nights thereafter. Despite these clear short-term benefits, however, doubt has been cast on whether or not DSIP treatment will prove to be of major benefit in long-term management of insomnia.

    Studies have been undertaken in patients suffering from the sleep apnoea syndrome and from narcolepsy. Unfortunately, no difference in DSIP concentrations has been found between those patients and normal patients [23]. DSIP may, paradoxically, be of use in the treatment of narcolepsy and it is possible that it exerts its effect by restoring circadian rhythms [24]. When single and multiple injections of DSIP were given in a controlled double-blind study, disturbed sleep was normalized and better performance and increased alertness was seen during awake cycles together with improved stress tolerance and coping behaviour [22].

    Non-sleep effects
    DSIP has been shown to have an anticonvulsant action in the rat. The threshold to NMDA- and picrotoxin-induced convulsions is increased by DSIP [25,26]. This anticonvulsant effect may undergo a diurnal variation with greater antiepileptic activity seen at night [27]. DSIP is not unique in possessing a diurnal variation in anticonvulsant activity as melatonin, b-endorphin and dexamphetamine all reduce seizure threshold during the day and it is possible that DSIP simply represents one of the endogenous controls of brain excitability [28]. DSIP has an antinociceptive action in mice, an effect which is blocked by naloxone [29].

    A neuroprotective effect has been demonstrated in rats subjected to bilateral carotid ligation [30]. A reduced mortality was observed together with a reduction in postischaemia function. DSIP also reduced brain swelling in a model of toxic cerebral oedema in the rat [31].

    DSIP attenuates emotional and psychological responses to stress and also reduces the central amine responses to stress in rats [32]. The action of corticotrophin releasing factor on the pituitary gland in the rat is attenuated with a consequential inhibition of pituitary adrenocorticotrophic hormone (ACTH) secretion [33]. The situation is less clear in man as although one study confirmed this finding [34] another reported no inhibitory effect on the adrenocortical axis to both physiological and stressor stimuli [35]. DSIP had no effect on growth hormone or prolactin concentrations when administered to human volunteers [36]. In one study, infusions of 3 or 4 mg (an enormous dose) had no effect on ACTH levels or on cortisol secretion [35] although in another study DSIP 25 nmol kg-1 significantly decreased ACTH concentrations [36].

    DSIP concentrations change during certain psychiatric disorders. Patients suffering from schizophrenia and depression have lower plasma and cerebrospinal fluid concentrations of DSIP than comparable normal volunteers [37]. Concentrations were also inversely correlated with sleep disturbance in those patients.

    As might be expected of any substance which is naturally occurring, side-effects are uncommon. Normally, concentrations would be very low and therefore the injection of large, probably non-physiological doses might be expected to at least produce some unwanted effect. No significant side-effects have so far been reported with DSIP. In some human studies, transient headache, nausea and vertigo have been reported. DSIP actually appears to be incredibly safe as its LD50 has never been determined because it has never so far proved possible to kill an animal whatever the dose of DSIP administered.

    Clinical uses
    Clinical uses for DSIP already exist. The agent has been used for the treatment of alcohol and opioid withdrawal with some success [38]. Clinical symptoms and signs disappear after injection of DSIP although some patients have reported occasional headaches.

    DSIP possesses a number of other apparently unrelated properties. In hypertensive rats, 200 μg kg-1 day-1of DSIP for 10 days had an antihypertensive effect [39]. DSIP has also been reported to possess antimetastatic activity [40]. It may also reduce amphetamine-induced hyperthermia and may be beneficial in some chronic pain conditions [41].

    An interesting study reported in 1986 injected DSIP and several analogues of the peptide directly into the cerebral ventricle of rats. DSIP did not increase sleep and this was thought to be due to its very rapid metabolism. However, two of the analogues did induce sleep but one produced arousal. It would appear therefore that there might be the potential for not only sleep but sleep reversal within the analogues of DSIP [42].

    The molecular sites for the action of anaesthetic agents are being identified. Volatile agents appear to act on specific sites of the GABA-A and glycine receptors, whereas ketamine and xenon act on the NMDA receptors. These sites are reproducible and clearly defined, but what is their natural purpose, as neither volatile anaesthetic agents nor xenon are usually found in physiological systems? It is possible, but has yet to be demonstrated, that DSIP and other neuroactive peptides selectively bind to these regions of GABA-A, glycine and/or NMDA receptors.

    Is DSIP of relevance to the anaesthesiologist?
    Anaesthesia is physiologically distinct from natural sleep and anaesthetic agents appear to work on receptor mechanisms normally dedicated to the control of brain metabolism. Conventional sleep staging does not indicate the depth of anaesthesia; rapid-eye movements (REM) and other characteristics of natural sleep are not seen during anaesthesia. It is possible, however, that anaesthesia is mimicking a natural phenomenon such as hibernation by copying the action of natural neuroactive peptides such as DSIP.

    What is the significance of DSIP to anaesthesia? Could DSIP be the body's natural anaesthetic? Is activation of the DSIP receptors related to the state of anaesthesia? These questions must remain speculative for the present. Whether or not DSIP is the body's natural anaesthetic, or a substance closely involved in this process, it may not prove to be possible to administer it in a way which could be regarded as anaesthesia. Could it therefore be used as the body's natural sedative? No studies have been performed to investigate this possible use although it would theoretically seem to have potential. http://journals.lww.com/ejanaesthesi...peptide.1.aspx
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    Journal of Clinical Endocrinology & Metabolism, Vol 78, 1085-1089, Copyright © 1994 by Endocrine Society
    Diurnal rhythm of plasma delta-sleep-inducing peptide in humans: evidence for positive correlation with body temperature and negative correlation with rapid eye movement and slow wave sleep
    TC Friedman, D Garcia-Borreguero, D Hardwick, CN Akuete, MK Stambuk, LD Dorn, MN Starkman, YP Loh and GP Chrousos

    Since delta-sleep-inducing peptide (DSIP) was isolated in 1977, numerous reports have suggested that this nonapeptide stimulates delta- sleep [slow wave sleep (SWS)]. Although DSIP-like immunoreactivity (DSIP-LI) has been found in the serum of many animals and man, its diurnal rhythm and relation to sleep stages have not been well defined. We hypothesized that circulating levels of this putative sleep hormone would be highest at night and would probably be elevated before or during episodes of SWS. We, therefore, measured plasma DSIP-LI levels every 30 min for 24 h in 12 normal volunteers in whom we obtained simultaneous polygraphic recordings. We found a distinct diurnal rhythm for plasma DSIP-LI levels, with the maximum at 1500 h and the minimum at 0100 h. DSIP-LI levels were substantially lower in rapid eye movement sleep (P < 0.005) and somewhat lower in SWS (P < 0.05) compared to awake values. DSIP-LI levels did not rise before, during, or after a significant percentage of episodes of SWS. We found, however, that the diurnal rhythm of DSIP-LI closely followed that of body temperature with a high degree of correlation (r2 = 0.66; P < 0.0001). We conclude that endogenous elevations of circulating DSIP may be associated with suppression of slow wave and rapid eye movement sleep, and that the circadian rhythm of this peptide is coupled directly or indirectly to that of body temperature. http://jcem.endojournals.org/cgi/con...ract/78/5/1085
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    well, i was having major sleeping issues and always been kind of down. And this is making a world of difference. Stress free all day long, sleep like a baby. Just need to take energy supplements to stay alert during day.
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    Eur Neurol 1984;23:372-385 (DOI: 10.1159/000115716)
    Therapeutic Effects of Delta-Sleep-Inducing Peptide (DSIP) in Patients with Chronic, Pronounced Pain Episodes
    A Clinical Pilot Study
    W. Larbiga, W.D. Gerberb, M. Klucka, G.A. Schoenenbergerc
    Experimental results suggested a modulation or 'programming' interaction of delta sleep-inducing peptide (DSIP) with endogenous opioid-peptidergic systems and exogenous intracerebrally or systemically administered morphine and amphetamine. The induction of cerebral MAO-A activity, a pronounced influence on the circadian rhythms of locomotion and intracerebral neurotransmitter as well as plasma protein and Cortisol concentrations has been reported. DSIP was also shown to counteract experimentally induced stress situations in animals. An improvement of the psychomotor performance and the concentration capacity in humans beside sleep normalization and pronounced effects on withdrawal symptoms including pain states in alcoholics and opiate addicts was discovered. This encouraged a pilot study for a possible action of the peptide in humans suffering from chronic pronounced pain episodes. We investigated the therapeutic effect in 7 patients with migraine episodes and vasomotor headaches, chronic tinnitus and psychogenic pain attacks. The anamnestic (baseline) values were statistically compared with the katamnestic control period. DSIP lowered significantly the pain levels of 6 out of 7 patients after intravenous administration on 5 consecutive days followed by 5 injections every 48-72 h. Remarkably, a simultaneous significant reduction of the concomitantly occurring depressive states was observed.
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    Originally Posted by NO HYPE View Post
    Journal of Clinical Endocrinology & Metabolism, Vol 78, 1085-1089, Copyright © 1994 by Endocrine Society
    Diurnal rhythm of plasma delta-sleep-inducing peptide in humans: evidence for positive correlation with body temperature and negative correlation with rapid eye movement and slow wave sleep
    TC Friedman, D Garcia-Borreguero, D Hardwick, CN Akuete, MK Stambuk, LD Dorn, MN Starkman, YP Loh and GP Chrousos

    Since delta-sleep-inducing peptide (DSIP) was isolated in 1977, numerous reports have suggested that this nonapeptide stimulates delta- sleep [slow wave sleep (SWS)]. Although DSIP-like immunoreactivity (DSIP-LI) has been found in the serum of many animals and man, its diurnal rhythm and relation to sleep stages have not been well defined. We hypothesized that circulating levels of this putative sleep hormone would be highest at night and would probably be elevated before or during episodes of SWS. We, therefore, measured plasma DSIP-LI levels every 30 min for 24 h in 12 normal volunteers in whom we obtained simultaneous polygraphic recordings. We found a distinct diurnal rhythm for plasma DSIP-LI levels, with the maximum at 1500 h and the minimum at 0100 h. DSIP-LI levels were substantially lower in rapid eye movement sleep (P < 0.005) and somewhat lower in SWS (P < 0.05) compared to awake values. DSIP-LI levels did not rise before, during, or after a significant percentage of episodes of SWS. We found, however, that the diurnal rhythm of DSIP-LI closely followed that of body temperature with a high degree of correlation (r2 = 0.66; P < 0.0001). We conclude that endogenous elevations of circulating DSIP may be associated with suppression of slow wave and rapid eye movement sleep, and that the circadian rhythm of this peptide is coupled directly or indirectly to that of body temperature. http://jcem.endojournals.org/cgi/con...ract/78/5/1085

    Is this negative or positive, btw thanks for digging up all this information.
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    ...
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    Originally Posted by NO HYPE View Post
    ...
    so the patients slept better and deeper?
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    Originally Posted by Mike83 View Post
    Is this negative or positive, btw thanks for digging up all this information.
    Sounds like a negative to me if it is preventing REM sleep.
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    Originally Posted by RatherBeLifting View Post
    Sounds like a negative to me if it is preventing REM sleep.
    Not if it induces delta-wave sleep and/or restores circadian rythm. I believe the delta-wave portion of SWS initiates body repair/regenerates tissues, builds bone/muscle, strengthens immune system, ect.
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    Originally Posted by Mike83 View Post
    gh responses to humans
    "DSIP had no effect on growth hormone or prolactin concentrations when administered to human volunteers" [36].

    Psychoneuroendocrinology
    Volume 18, Issue 1, 1993, Pages 79-84
    Delta sleep-inducing peptide administration does not influence growth hormone and prolactin secretion in normal women
    M. Giusti, A. Carraro, E. Porcella, S. Valenti, D. Nicora, P. Sessarego and G. Giordano

    The aim of this study was to analyze the effects of delta sleep-inducing peptide (DSIP) on growth hormone (GH) and prolactin (PRL) secretion in eight healthy women with normal cycles (aged 17–36 years). GH and PRL secretion was studied in five women after DSIP (25 µg/kg bw IV over 30 min), arginine chlorhydrate (0.5 g/kg bw IV over 30 min) and simultaneous DSIP plus arginine chlorhydrate administration. In three other women the circadian rhythm of GH and PRL was studied during DSIP (25 µg/kg bw from 2130h to 2230h) and placebo IV infusion. Serum GH and PRL levels were normal under basal conditions and no effects were noted after the infusion of DSIP. The GH and PRL circadian rhythm was not modified by DSIP administration. DSIP did not influence GH and PRL responsiveness to arginine chlorhydrate. We found that at dosages which are known to modify ECG patterns, DSIP is unable to modify spontaneous or arginine chlorhydrate-induced GH and PRL secretion.
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    Awesome posts! As i can say, this is an amazing peptide that has helped me dramatically. I was told today in the gym by a gym guru, I look better than i ever have, and what i was taking (not on anything lol)

    My sleep patterns were very screwed up and could never sleep properly it seemed, but now it seems to be restored and enhanced!!!!
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    if you are interested in a long read, this is a in depth very informative pdf file of studies on this peptide.

    http://content.karger.com/ProdukteDB...ame=115711.pdf
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    Just wanted to see if anyone else has tried this yet?

    Any how did you like it?

    An update on my behalf, I think this is only good short term, it was great at first but lost it efficiency after awhile.
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    Registered User Mike83's Avatar
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    bringing this back from the dead. I have not used this stuff in months and plan on trying again. I hope it works like it use to, at first it was amazing then I seemed to be immune to it or it made me not be able to sleep. Also, the more empty your stomach, the better, which is hard to do usually. But i remember, when i had a real empty gut and used this stuff, i slept amazing.

    Bringing it back to see if anyone else has used it.
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    Registered User GoM999's Avatar
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    Originally Posted by Mike83 View Post
    bringing this back from the dead. I have not used this stuff in months and plan on trying again. I hope it works like it use to, at first it was amazing then I seemed to be immune to it or it made me not be able to sleep. Also, the more empty your stomach, the better, which is hard to do usually. But i remember, when i had a real empty gut and used this stuff, i slept amazing.

    Bringing it back to see if anyone else has used it.
    Just tried this stuff as I have terrible trouble sleeping; I think it's probably the biggest limiting factor to my growth. Tried all the natural stuff and more.

    I mixed 5mg with 3 ml BW and injected about 10 ticks an hour before bed. So about 167+ mcgs, which made me groggy after about 20 minutes, but seemed to subside a bit before I hit the sac. I did get to sleep fairly quickly, but still woke up early and had trouble (hours) getting back to sleep. I was a little dopey this morning, but I got up late, so this passed fairly quickly.

    I think I'll go to 15 ticks about 30 minutes before bed to see what happens.

    I did read somewhere that this stuff is supposed to have a benficial effect for several days, which would seem to indicate that subsequent doses would improve your sleep patterns. Any experience with this?
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    Originally Posted by Mike83 View Post
    I have been testing this through a lab rat and it works amazing!!!!!!! I believe there is a massive gh output through some channels. Body comp changing amazing fast and sleeping better than ever.
    If it works for people, I need this.... it will be like crack for me. I can't sleep for ish, and sleep is a key factor in body building and health.
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    Registered User GoM999's Avatar
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    Originally Posted by TrueAmateur View Post
    If it works for people, I need this.... it will be like crack for me. I can't sleep for ish, and sleep is a key factor in body building and health.
    Yeah, I'm not sure what to make of it. It did not seem to help the first few times I tried it; it did not help me sleep longer or better and seemed to raise my BP. So I laid off for a few days and tried it on the WE again when I have a better chance to sleep. I did NOT sleep longer, but I did seem to sleep better.

    I must have OD'd a bit the last few days as my bottom BP # dropped and I feel a little groggy, but I slept through the night for the first time in years.

    I'm going to try some GH next for sleep and regenration issues, but the DSIP is definitely cheaper! :-)
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    Anyone have more info on this? I'm considering asking my doc about it if it really does restore sleep patterns or natural ability to fall asleep. Any thoughts there?
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    Originally Posted by chimeranD View Post
    Anyone have more info on this? I'm considering asking my doc about it if it really does restore sleep patterns or natural ability to fall asleep. Any thoughts there?
    Wouldn't waste your or your doctor's time. Feedback on DSIP overall seems to be lackluster at best...
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    Just curious as to if you guys have tried any prescription meds for sleep in the past. Obviously there are once's that are hypnotics (ambien, lunesta).. have you tried Rozerem? It has been shown to help people sleep through different pathway then the usual GABA receptor drugs.
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