Emideltide (DSIP) Interactions with CNS Neurotransmitters

Emideltide, or Delta Sleep-Inducing Peptide (DSIP), is an endogenous peptide with nine amino acids. In relevant studies, the peptide was initially isolated from the central nervous system (CNS) of research models undergoing electrically induced sleep in laboratory settings. The precise biological functions of Emideltide remain incompletely understood. Still, it is hypothesized that the peptide might impact sleep architecture—the organization and cyclic patterns observed during sleep—and possibly support sleep quality in research models through interactions with specific structures within the CNS.

These potential impacts include reducing the time it takes for research models under observation to transition from wakefulness to sleep and supporting overall sleep quality. The mechanisms by which Emideltide might mediate such impacts remain speculative, but it is thought that modulation of several neurotransmitters within central nervous system models may play a role. Specific neurotransmitters involved are posited to include the  N-methyl-D-aspartate (NMDA) receptors, the gamma-aminobutyric acid (GABA) receptors, the opioid receptors, and the alpha 1-adrenergic receptor. Below, we will break down the mechanisms of Emideltide, interactions with these receptors, and potential relevant laboratory impacts.

 

Research

Emideltide Potential Actions on NMDA and GABA Receptors

Research by Grigor’ev et al. posits that Emideltide may interact with both NMDA and GABA receptors in experimental neuronal preparations.⁽¹⁾ NMDA receptors are associated with glutamate, which is considered an essential excitatory neurotransmitter. In contrast, GABA receptors are linked to inhibitory neurotransmission, which may be crucial for reducing neural activity and inducing a relaxed state. Emideltide is thought to support the responses mediated by GABA receptors in various regions of brain models, which might ultimately contribute to the sleep-inducing potential observed in earlier experiments.

This potentiation of GABA receptor activity suggests that Emideltide may promote inhibitory signaling within central nervous system models. Conversely, Emideltide is believed to exert an inhibitory impact on NMDA receptor-mediated currents. Emideltide is thought to reduce the excitatory responses associated with NMDA receptor activation in cortical and hippocampal neurons. Additionally, data from calcium uptake experiments indicates that Emideltide may interfere with NMDA receptor function at presynaptic sites. This points to potential further support for its modulatory role in excitatory neurotransmission.

Further research by Sudakov et al. suggests that “Emideltide effects on the neuronal activity in the sensorimotor brain cortex, dorsal hippocampus, ventral anterior thalamic nucleus and lateral hypothalamus might be mediated by the NMDA-receptors.”⁽²⁾ Specifically, Emideltide appears to diminish the excitatory impact of glutamate, which may be posited as a consequence of Emideltide binding to or otherwise altering NMDA receptor function. Moreover, when NMDA receptor activity is attenuated using a non-competitive antagonist, the actions of Emideltide on neuronal activation are notably reduced, thereby supporting the theory about Emideltide interacting with these receptors. Due partly to its potential interactions with NDMA and GABA receptors, Emideltide may also interact with related neuropeptides.

Additional research by Sudakov et al. suggests that Emideltide may interact with neuropeptides involved in stress responses, including Substance P, beta-endorphin, and corticosterone.⁽³⁾ In research models, Emideltide seems to contribute to increased Substance P levels in both the hypothalamus and plasma. At the same time, it initially decreases beta-endorphin levels before later increasing them. In addition, Emideltide is believed to reduce corticosterone levels, which are commonly elevated in stressed research models. These combined impacts indicate that Emideltide might attenuate stress responses by altering multiple signaling pathways.

Emideltide Potential Actions on Adrenergic Receptors

Research by Graf et al. suggests that Emideltide might interact with the adrenergic system in the pineal gland by modulating the alpha-1 adrenergic receptors.^(4} More specifically, Emideltide boosts the gland’s response to hormones like norepinephrine, which normally increases the activity of an enzyme involved in pineal function called N-acetyltransferase.

This exposure to Emideltide is posited to contribute to an even more substantial N-acetyltransferase activation, and the main site of interaction between the pineal gland and the peptide appears to be the alpha-1 adrenergic receptors. Thus, these findings imply that Emideltide might potentially modulate the responsiveness of the alpha-1-adrenergic receptor, thereby impacting downstream processes such as N-acetyltransferase activity. Graf et al. posited that this “mechanism may also be responsible for other biological activities of Emideltide such as sleep-induction and stress-tolerance.”

Emideltide Potential Actions on Opioid Signaling

Research by Nakamura et al. proposes that Emideltide may indirectly interact with the opioid system.⁽⁵⁾ Binding assays using radiolabeled opioid ligands have suggested that Emideltide does not displace endogenous ligands from opioid receptors and does not act as a direct agonist at these receptor sites. Instead, experiments with brainstem tissue slices have suggested that Emideltide may stimulate the release of endogenous opioid peptides, such as Met-enkephalin.

This increase in peptide release is concentration-dependent and may contribute to the antinociceptive potential proposed by some Emideltide studies. Instead of binding directly to opioid receptors, Emideltide may modulate the endogenous opioid system by supporting the availability of endogenously occurring opioid peptides. This indirect mechanism of action provides a potential explanation for the analgesic properties attributed to Emideltide in laboratory settings. Researchers such as Dick et al. also suggest that via these interactions, Emideltide may have promise in laboratory models of withdrawal and disturbed sleep patterns.⁽⁶⁾

Emideltide Potential Actions on Serotonin Signaling and Sleep Patterns

Schneider-Helmert and colleagues have observed that Emideltide may alter the organization of sleep in research models, particularly by interacting with one of the phases of sleep known as slow-wave sleep (SWS) or the S3 phase.⁽⁷⁾ Emideltide is posited to reduce the latency to deep slow-wave sleep and increase the overall duration of SWS, primarily by prolonging individual SWS episodes rather than increasing the frequency. This reorganization is suggested to mediate a significant reduction of wakefulness during the recording period, while REM (S4) sleep may remain largely unaffected. The selective support of SWS suggests that Emideltide acts as a neuromodulator by promoting greater cortical synchronization during sleep.

The observed impacts—including a shift toward deeper, more consolidated slow-wave sleep—are in some ways reminiscent of the changes seen with manipulations known to increase brain serotonin levels. Given that better-supported serotonergic activity is correlated with increased SWS, it is plausible that Emideltide may interact with or otherwise impact serotonergic pathways, thereby contributing to its sleep-facilitating properties. More recent research by Kovalzon et al. has suggested that the peptide may lead to an immediate increase in sleep pressure and about a 59% increase in sleep occurrence within two hours of initiating Emideltide experimentation.⁽⁸⁾ The scientists also posited that the peptide may have better-supported sleep efficiency by theoretically shortening sleep onset.

You can find DSIP for sale with 99% purity, on our website (available for research use only).

NOTE: These products are intended for laboratory research use only. This peptide is not intended for personal use. Please review and adhere to our Terms and Conditions before ordering.

 

References:

1. Grigor’ev VV, Ivanova TA, Kustova EA, Petrova LN, Serkova TP, Bachurin SO. Effects of delta sleep-inducing peptide on pre- and postsynaptic glutamate and postsynaptic GABA receptors in neurons of the cortex, hippocampus, and cerebellum in rats. Bull Exp Biol Med. 2006 Aug;142(2):186-8. English, Russian. doi: 10.1007/s10517-006-0323-9. PMID: 17369935
2. Sudakov KV, Umriukhin PE, Rayevsky KS. Delta-sleep inducing peptide and neuronal activity after glutamate microiontophoresis: the role of NMDA-receptors. Pathophysiology. 2004 Oct;11(2):81-86. https://pubmed.ncbi.nlm.nih.gov/15364118/
3. Sudakov KV, Coghlan JP, Kotov AV, Salieva RM, Polyntsev YuV, Koplik EV. Delta-sleep-inducing peptide sequels in the mechanisms of resistance to emotional stress. Ann N Y Acad Sci. 1995 Dec 29;771:240-51. doi: 10.1111/j.1749-6632.1995.tb44685.x. PMID: 8597403.
4. Graf MV, Schoenenberger GA. Delta sleep-inducing peptide modulates the stimulation of rat pineal N-acetyltransferase activity by involving the alpha 1-adrenergic receptor. J Neurochem. 1987 Apr;48(4):1252-7. doi: 10.1111/j.1471-4159.1987.tb05654.x. PMID: 3029331.
5. Nakamura A, Nakashima M, Sakai K, Niwa M, Nozaki M, Shiomi H. Delta-sleep-inducing peptide (DSIP) stimulates the release of immunoreactive Met-enkephalin from rat lower brainstem slices in vitro. Brain Res. 1989 Feb 27;481(1):165-8. doi: 10.1016/0006-8993(89)90498-8. PMID: 2706459.
6. Dick P, Grandjean ME, Tissot R. Successful treatment of withdrawal symptoms with delta sleep-inducing peptide, a neuropeptide with potential agonistic activity on opiate receptors. Neuropsychobiology. 1983;10(4):205-8. doi: 10.1159/000118012. PMID: 6328354.
7. Susić V, Masirević G, Totić S. The effects of delta-sleep-inducing peptide (DSIP) on wakefulness and sleep patterns in the cat. Brain Res. 1987 Jun 30;414(2):262-70. https://pubmed.ncbi.nlm.nih.gov/3620931/
8. 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 Aug;19(8):341-5. https://pubmed.ncbi.nlm.nih.gov/6895513/