Melatonin vs PT-141 (Bremelanotide)

Melatonin

Melatonin (N-acetyl-5-methoxytryptamine) is a small indoleamine made from tryptophan, chiefly in the pineal gland; it is not a peptide. It is made from serotonin in two steps, acetylation and then methylation, in the pineal gland and in smaller amounts in the retina, gut and other tissues. Pineal production follows a daily rhythm set by the suprachiasmatic nucleus of the hypothalamus: it rises in darkness and is suppressed by light. Human research is substantial and concentrates on circadian physiology and sleep, alongside a large animal literature that includes seasonal breeding. Work on its chemistry as a free-radical scavenger is mostly in vitro or in animals, often at concentrations well above those found in blood.

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 Melatonin acts

Two high-affinity melatonin receptors, MT1 and MT2, have been characterised. Both are G-protein-coupled receptors that couple mainly to Gi, lowering cyclic AMP, and both are expressed in the suprachiasmatic nucleus, where rodent studies have linked MT1 to suppression of neuronal firing and MT2 to shifts in the timing of the circadian clock. They are also found in the retina, blood vessels and several peripheral tissues. A third binding site, once labelled MT3, was later identified as the enzyme quinone reductase 2. Apart from receptor signalling, melatonin and several of its metabolites react directly with reactive oxygen and nitrogen species in chemical systems.

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: Melatonin, Amino acid derivative (non-peptide); PT-141 (Bremelanotide), Melanocortin receptor agonist (cyclic heptapeptide)
• Length: Melatonin, not recorded; PT-141 (Bremelanotide), 7 amino acids
• Molecular weight: Melatonin, 232.28 g/mol; PT-141 (Bremelanotide), 1025.2 g/mol
• Molecular formula: Melatonin, C13H16N2O2; 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.