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Delta-Sleep-Inducing Peptide (DSIP)

Delta-Sleep-Inducing Peptide (DSIP) October 5, 2020

Delta-Sleep-Inducing Peptide (DSIP) was first proposed as a sleep-peptide and this remains the prevalent impression of its function. Since normal people spend about one-third of their lifetime sleeping (about 25 years), it is rather surprising that the phenomenon of sleep and its purpose, which is still in question, has been long overlooked as a topic of scientific interest. A decisive step forward was made between 1928 and 1938 when H. Berger described the electroencephalogram (EEG) of man. After this, the EEG became the main tool used for the characterization of sleep and, subsequently, electrostimulation of the brain became the predominant way to influence it. Sleep induction by intracranial electrostimulation represented the “dry way” compared to the “wet way” by infusion of humoral factors into the body. A broad variety of such factors have been shown to induce sleep or sleep-like behavior, including small organic molecules like tryptophan as well as macromolecular proteins

The isolation and characterization in the brain of peptides regulating the release of hormones at very low concentrations, and thus influencing basic body functions, has encouraged the search for similar factors responsible for sleep-control. Only one decade ago, the prevalent view was that sleep regulation was merely a question of the cooperation of the different neurotransmitter systems, especially serotonin (5HT). In recent years, however, the idea has become widely accepted that peptides may play an important role in the organization of sleep, although these functions are not yet clarified.

Delta-Sleep-Inducing Peptide (DSIP) was first proposed as a sleep-peptide and this remains the prevalent impression of its function. Since normal people spend about one-third of their lifetime sleeping (about 25 years), it is rather surprising that the phenomenon of sleep and its purpose, which is still in question, has been long overlooked as a topic of scientific interest. A decisive step forward was made between 1928 and 1938 when H. Berger described the electroencephalogram (EEG) of man. After this, the EEG became the main tool used for the characterization of sleep and, subsequently, electrostimulation of the brain became the predominant way to influence it. Sleep induction by intracranial electrostimulation represented the “dry way” compared to the “wet way” by infusion of humoral factors into the body. A broad variety of such factors have been shown to induce sleep or sleep-like behavior, including small organic molecules like tryptophan as well as macromolecular proteins

The isolation and characterization in the brain of peptides regulating the release of hormones at very low concentrations, and thus influencing basic body functions, has encouraged the search for similar factors responsible for sleep-control. Only one decade ago, the prevalent view was that sleep regulation was merely a question of the cooperation of the different neurotransmitter systems, especially serotonin (5HT). In recent years, however, the idea has become widely accepted that peptides may play an important role in the organization of sleep, although these functions are not yet clarified.

Thus it appears that endogenous DSIP [or DSIP‐like peptide(s)] is a typical regulatory peptide and should therefore play an important role in endocrine regulation. Indeed, although data on the direct effects of DSIP upon noradrenergic, serotonergic, and GABA‐ergic transmission in the brain are not consistent (Lysenko et al. 1995; Strekalova 1998), it was shown that DSIP:

  • Decreases the basal corticotropin level and blocks its release evoked by corticoliberin injection
  • Stimulates the secretion of luteinizing hormone
  • Stimulates the release of somatoliberin and somatotropin and inhibits somatostatin secretion
  • Responses to stress, where DSIP acts as a previously unknown stress‐limiting factor
  • Immune responses, where it can play the role of immunomodulator, cell differentiation factor, and anti-tumor agent
  • DSIP has also been shown to have hypothermic properties (DSIP was demonstrated to have an enchanting effect on serotonin‐, apomorphine‐ and opioid‐induced hypothermia
  • Cardiotropic and vasomotor activity (DSIP can normalize blood pressure and myocardial contraction
  • Pain, where DSIP can produce an analgesic effect by augmenting met‐encephalin binding with opiate receptors
  • Regulation of diurnal and circadian rhythmicity
  • Anti‐opioid and anti‐alcohol activity (DSIP can suppress the development of alcohol and opiate dependency this being the basis for DSIP clinical application
  • Anticonvulsive effects
  • Antioxidant effects

Successful treatment of withdrawal symptoms with delta sleep-inducing peptide, a neuropeptide with potential agonistic activity on opiate receptors

It has been postulated that delta sleep-inducing peptide (DSIP) possesses an agonistic activity on opiate receptors and might be of value in the treatment of withdrawal syndromes. To test this hypothesis, DSIP (25 nmol/kg) was injected intravenously as the sole treatment to 67 patients presenting withdrawal symptoms (28 from ethyl alcohol, 39 from opiates). 27% of the patients were lost or unsuitable for evaluation. From the 49 evaluable patients, DSIP produced a beneficial effect in 48 (22 alcoholics and 26 from 27 opiate addicts), with an immediate onset of action, a good and lasting suspension of the somatic symptoms and signs. Anxiety resolved more slowly, within hours. No major side-effect occurred. DSIP offers a new physiologically-based approach for the treatment of established withdrawal syndrome.

Therapeutic effects of a delta-sleep-inducing peptide (DSIP) in patients with chronic, pronounced pain episodes. A clinical pilot study

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 besides sleep normalization and pronounced effects on withdrawal symptoms including pain states in alcoholics and opiate addicts was discovered. This encouraged a pilot study for 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.

References: PMID: 6328354, PMID: 6548970, PMID: 16539679

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