Oxytocin vs PT-141 (Bremelanotide)

Oxytocin

Oxytocin is a nine-residue peptide hormone, cyclised by a disulphide bond between its two cysteines and amidated at the C-terminus. It is made by neurons of the hypothalamus and released both from the posterior pituitary into the circulation and within the brain. It differs from vasopressin at two of its nine positions, and their receptors belong to one family. Its classical physiological roles, in uterine contraction and milk ejection, were established first, and in the 1950s it became the first peptide hormone to be synthesised in the laboratory. More recent research concerns its signalling in the brain and social behaviour; the animal literature is substantial, while human findings have been inconsistent and remain debated.

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 Oxytocin acts

The oxytocin receptor (OXTR) is a class A G-protein-coupled receptor that signals mainly through Gq/11, activating phospholipase C and raising intracellular calcium; coupling to other G proteins has also been reported. It is expressed in the myometrium, mammary myoepithelial cells and several brain regions, among other tissues, and uterine expression rises sharply late in pregnancy. Because oxytocin and vasopressin are so alike, each can act at the other's receptors at higher concentrations, and oxytocin has measurable activity at the vasopressin V1a receptor. How much oxytocin in the circulation crosses into the brain is still debated.

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: Oxytocin, Cyclic nonapeptide hormone (neurohypophysial peptide); PT-141 (Bremelanotide), Melanocortin receptor agonist (cyclic heptapeptide)
• Length: Oxytocin, 9 amino acids; PT-141 (Bremelanotide), 7 amino acids
• Molecular weight: Oxytocin, 1007.2 g/mol; PT-141 (Bremelanotide), 1025.2 g/mol
• Molecular formula: Oxytocin, C43H66N12O12S2; PT-141 (Bremelanotide), C50H68N14O10
• Half-life: Oxytocin, Plasma half-life of oxytocin ranges from 3 to 20 min.; PT-141 (Bremelanotide), not recorded

Reading a comparison

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