DSIP (Delta Sleep-Inducing Peptide) vs PT-141 (Bremelanotide)

DSIP (Delta Sleep-Inducing Peptide)

DSIP, or delta sleep-inducing peptide, is a nine-residue peptide first described in rabbits during experimentally induced sleep. It was isolated from blood drawn from animals in which sleep had been produced by electrical stimulation of the brain, and the name comes from the slow-wave activity reported when that material was transferred to other animals. Later studies in animals and small human studies gave inconsistent findings on sleep, and the name describes how the peptide was found rather than an agreed function. No gene encoding DSIP and no dedicated receptor have been found. Work continued on its possible roles in stress hormones and other systems, but the literature is fragmented, and much of it is several decades old.

PT-141 (Bremelanotide)

PT-141 (bremelanotide) is a synthetic cyclic heptapeptide melanocortin receptor agonist, closely related in structure to melanotan II. The two share the same seven residues and the same lactam bridge between aspartic acid and lysine; they differ only at the C-terminus, which in PT-141 is a free carboxylic acid rather than an amide. Inside the ring sits His-D-Phe-Arg-Trp, the sequence through which melanocortin peptides engage their receptors. Its receptor pharmacology has been characterised in binding and cell-signalling assays and in animal studies, and it has also been the subject of human clinical research. Mechanistic work has concentrated on its action at MC4R in the brain.

How DSIP (Delta Sleep-Inducing Peptide) acts

Without an identified receptor or gene, DSIP's standing as a signalling molecule in its own right is uncertain, and its mechanism is described through scattered observations. Animal and tissue studies have reported interactions with GABA and glutamate transmission, including NMDA receptors, with opioid signalling, and with the hypothalamic–pituitary–adrenal axis, where release of ACTH and corticosterone has been examined. Immunoreactive material resembling DSIP has been reported in the brain and in peripheral tissues. These reports come from different models and methods, and no single pathway has emerged that ties them together.

How PT-141 (Bremelanotide) acts

Bremelanotide has been reported to activate several melanocortin receptor subtypes, including MC1R, MC3R, MC4R and MC5R, so it is not selective for one. These receptors are G-protein-coupled and signal mainly through Gs and cyclic AMP. MC3R and MC4R are expressed in the hypothalamus and elsewhere in the central nervous system, where their endogenous agonists are α-MSH and related melanocortins and where agouti-related peptide acts as an antagonist and inverse agonist. It shares this lack of subtype selectivity with melanotan II, from which it differs by a single terminal group.

The records side by side

• Type: DSIP (Delta Sleep-Inducing Peptide), Nonapeptide; PT-141 (Bremelanotide), Melanocortin receptor agonist (cyclic heptapeptide)
• Length: DSIP (Delta Sleep-Inducing Peptide), 9 amino acids; PT-141 (Bremelanotide), 7 amino acids
• Molecular weight: DSIP (Delta Sleep-Inducing Peptide), 848.8 g/mol; PT-141 (Bremelanotide), 1025.2 g/mol
• Molecular formula: DSIP (Delta Sleep-Inducing Peptide), C35H48N10O15; PT-141 (Bremelanotide), C50H68N14O10

Reading a comparison

A comparison places two records side by side; it does not merge them. Each description above is drawn from that compound's own record, and the two were not necessarily characterised by the same methods, at the same time, or to the same level of detail. Before comparing any attribute, it is worth establishing that both records describe the substance you think they describe — names are not identifiers, and two entries sharing a name can differ in salt form, stereochemistry or the convention used to state a mass. Where a figure carries no method beside it, the comparison is between two reported numbers rather than between two measurements.