DSIP

DSIP (Delta Sleep-Inducing Peptide) is a naturally occurring nonapeptide with the amino acid sequence Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu. First isolated from the cerebral venous blood of rabbits during electrically induced slow-wave sleep, DSIP has been shown to promote delta wave (Stage 3/4) sleep — the deepest and most restorative phase of the sleep cycle. Unlike conventional sleep medications that broadly suppress neural activity, DSIP appears to modulate the natural sleep architecture, promoting deep sleep while preserving REM patterns.

Beyond its sleep-promoting effects, DSIP has demonstrated a remarkably diverse range of biological activities. It modulates the hypothalamic-pituitary-adrenal (HPA) axis, reducing cortisol and ACTH release during stress. It influences pain perception through interactions with opioid systems, has been shown to normalize blood pressure in hypertensive models, and may offer neuroprotective effects during oxidative stress. This breadth of activity has led researchers to characterize DSIP as a regulatory peptide with homeostatic functions rather than a simple sleep-inducing agent.

Despite decades of research and clinical interest, DSIP remains an enigmatic peptide. Its mechanism of action is not fully understood, and it has not been definitively assigned to a specific receptor system. The peptide is rapidly degraded by aminopeptidases in the bloodstream, with a half-life of only 7-8 minutes, yet its physiological effects persist for hours. This disconnect between pharmacokinetic and pharmacodynamic profiles suggests that DSIP triggers lasting changes in gene expression or neuromodulatory cascades rather than acting through sustained receptor occupancy.

DSIP was discovered in 1974 by the Swiss researchers Marcel Monnier and Guido Schoenenberger at the University of Basel. They isolated it from the cerebral venous blood of rabbits during electrically induced slow-wave sleep, naming it for its ability to induce delta wave (deep) sleep in recipient animals. The nonapeptide sequence (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) was fully characterized by 1977. Extensive research followed throughout the 1980s and 1990s, revealing effects far beyond sleep induction, including stress modulation, pain threshold alteration, and hormonal regulation. The peptide was marketed as Deltaran in some countries. Despite decades of research, DSIP's mechanism of action remains incompletely understood, leading Kovalzon and Strekalova to describe it as "a still unresolved riddle" in their 2006 review.