In a rabbit study, the natural sleep peptide DSIP mostly didn’t change sleep, but two modified versions ([NMeAla2]DSIP and [Pro2]DSIP) modestly boosted deep (slow‑wave) sleep by about 10‑15%. One other version actually reduced sleep and raised body temperature. The effects likely depend on how the molecules are shaped and how resistant they are to breakdown.

The sleep-inducing activity of Delta Sleep-Inducing Peptide (DSIP) and its 13 synthetic analogs has been studied on rabbits with preliminary implanted electrodes. The peptides were injected into the lateral ventricle of cerebrum. Polygraphic computer monitoring of sleep-wake states was carried out at daytime for 7-12 h. DSIP and most analogs had no statistically significant effect on sleep compared to the control administration of saline to the same animals. [NMeAla2]DSIP and [Pro2]DSIP had a pronounced sleep-inducing effect and reliably increased the proportion of slow-wave sleep by 10-15% on average compared to the control. Several other analogs had a week sleep-inducing effect, increasing the proportion of slow-wave sleep during specific recording time only. [beta-Ala2]DSIP significantly suppressed sleep. In addition, this analog, as well as parent DSIP and four proline-containing nonapeptides, slightly increased the body temperature. The revealed differences may be due to both conformation properties and proteolytic resistance of the studied molecules, and it may reflect their indirect involvement in the control sleep-wake hormonal processes.