Successful Treatment of Withdrawal Symptoms with Delta Sleep-Inducing Peptide, a Neuropeptide with Potential Agonistic Activity on Opiate Receptors

Dick, P.; Grandjean, Monique; Tissot, R

doi:10.1159/000118012

Cited by 14 publications

(3 citation statements)

References 4 publications

(4 reference statements)

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“…It does not necessarily correspond completely to the functions of endogenous DSIP at normal levels, nor does it limit the possible use fulness of DSIP in neurochemically abnormal conditions. Our above cited trial with 2 patients on benzodiazepine withdrawal yielded results comparable to observations in a clinical study with addicts [4], indicating that DSIP may be of value in withdrawal syndromes [54]. These and other possible clinical applications need further explora tion, whereas a revolutionary treatment for sleep distur bances seems to be near at hand.…”

Section: Synthesissupporting

confidence: 64%

Effects of DSIP in Man

Schneider-Helmert¹,

Schoenenberger²

1983

Neuropsychobiology

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Animal experiments confirmed the neuropeptide nature of delta-sleep-inducing-peptide (DSIP) and a species-specific sleep promotion. Five different human studies were carried out with single and repeated intravenous injections of DSIP under double-blind conditions, and with assessing treatment effects by psychophysiological tests and polygraphic recordings. Compatibility of DSIP was good. Slow injection proved essential. A latency of sleep induction of 1 h, but a duration of up to 20 h was found. The somnogenic properties, initially proven in animal studies, were confirmed. Indications of specific effects on chronobiological regulations were found. A complete normalization of disturbed sleep was achieved by four consecutive injections to insomniacs. During the active awake state, DSIP induced higher alertness and better performance. Psychological tests and evaluation by psychotherapists indicated modulation of ego functions by DSIP in the direction of improved stress tolerance and coping ability. The various actions of DSIP might be conceptualized neurophysiologically on the level of ‘programming’ behavior by means of changing ‘local vigilances’. Whereas the somnogenic actions of DSIP appear promising for treating insomnia, other therapeutic perspectives in the field of psychiatry have to be explored.

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Section: Synthesissupporting

confidence: 64%

Effects of DSIP in Man

Schneider-Helmert¹,

Schoenenberger²

1983

Neuropsychobiology

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“…Administration of DSIP to rabbits [Monnier et al, 1977], rats [Kafi et al, 1979], cats [Pole et al, 1978], mice [Nagasaki et al, 1980] and humans [Schneider-Helmert et al, 1981a, b] confirmed the action of DSIP on sleep, monitored by electroencephalogram: the increase of sleep induced by DSIP is suppressed by the administration of the opiate antagonist Naloxone [Tissol, 1981], These studies show that DSIP, administered peripher ally, has a central action; the suggestion that this peptide crosses the blood-brain barrier has been experimentally confirmed [Kastin et al, 1981c;Banks ex al., 1982], Besides its effects on sleep, DSIP seems to interfere with such other homeostatic mechanisms as thermoregu lation [Yehuda and Kastin, 1980] and motor activity [Graf et al, 1981], The therapeutic use of DSIP in humans has shown promise for the treatment of insom nia [Schneider-Helmert et al, 1981a, b] and of the alco- hoi and opiate addiction withdrawal syndromes [Dick et al, 1982], However, the mechanism of action of DSIP is still unknown. Does it simply act upon endorphin recep tors, enkephalin receptors, etc., or are there specific DSIP systems in the brain?…”

Section: Introductionmentioning

confidence: 99%

Delta Sleep-Inducing Peptide in the Rat Brain: An Immunohistological Microscopic Study

Constantinidis¹,

Bouras²,

Guntern³

et al. 1983

Neuropsychobiology

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The authors have developed a method which makes it possible, for the first time, to visualize the delta sleep-inducing peptide in histological preparations and study it under the light and fluorescence microscope. Their research builds on Monnier’s discovery, in 1963, of a humoral hypnogenic factor in rabbits which was subsequently isolated and identified as a nonapeptide. Dubbed delta sleep-inducing peptide (DSIP), this factor was later detected in rat brain by radioimmunoassay but has eluded histological visualization until recently. In their work, the authors used an anti-DSIP antiserum suitable for immunohistological purposes. Two indirect immunohistological methods (PAP and immunofluorescence) allowed them to visualize, for the first time, structures containing specific DSIP-like immunoreactivity in some areas of the rat brain: indusium griseum, nucleus septi lateralis, hippocampus, striae longitudinales of Lancisi, bandeletta diagonalis of Broca, pallidum, hypothalamus, hypophysis and neocortex. Some DSIP pathways seem likely: (1) indusium griseum – striae longitudinales – hippocampus; (2) nucleus septi lateralis – striae longitudinales, bandeletta diagonalis – hippocampus; (3) neurons of the pyramidal layer of the hippocampus – gyms dentatus; (4) pallidum – commissura of Ganser – hypothalamus. The possible correlations between DSIP neurons and neurons with other neurotransmitters are discussed. In preliminary clinical trials, DSIP has shown promise for the treatment of insomnia and the opiate and alcohol withdrawal syndromes. Apart from the influence of DSIP on sleep and its possible role in addiction, the authors discuss the part which may be played by the limbic DSIP systems in instinctive-affective and memory mechanisms, and their possible involvement in psychosis and Alzheimer’s disease. Studies on DSIP have opened up new perspectives for research on the mechanisms of sleep, memory, drug addiction"(and possibly even of psychosis and Alzheimer’s disease) and their treatment.

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“…[10][11][12] Finally, it has been postulated that DSIP modulates endogenous opioid-peptidergic systems and exogenous intracerebrally or systemically administered morphine. [13][14][15][16] Unfortunately, its mechanisms of action have never been fully determined. The objective of looking for a binding site for DSIP prompted us to investigate the synthesis of [ …”

Section: Introductionmentioning

confidence: 99%

Synthesis of tritium labelled delta sleep‐inducing peptide

Giraud¹,

Morgat²,

Cavelier³

et al. 2001

Labelled Comp Radiopharmac

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SummaryThe a,b-dehydro precursor of the delta sleep-inducing peptide (DSIP) for tritiation was prepared prior to tritiation using a 3+6 fragment coupling strategy on a solid support. The first fragment, a,b-dehydrotripeptide, was prepared in solution in five steps in 79% overall yield while the second fragment was obtained by a step by step peptide synthesis on a Wang resin using an Fmoc strategy. The a,b-dehydrotripeptide was coupled to the fragment linked to the resin, followed by a deprotection/cleavage step to yield the a,b-dehydro-DSIP, 7. Catalytic reduction of unsaturated DSIP using tritium gas and palladium oxide as catalyst gave [ 3 H]DSIP having a specific activity of 1.184 TBq/mmol(32 Ci/mmol).

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Successful Treatment of Withdrawal Symptoms with Delta Sleep-Inducing Peptide, a Neuropeptide with Potential Agonistic Activity on Opiate Receptors

Cited by 14 publications

References 4 publications

Effects of DSIP in Man

Effects of DSIP in Man

Delta Sleep-Inducing Peptide in the Rat Brain: An Immunohistological Microscopic Study

Synthesis of tritium labelled delta sleep‐inducing peptide

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