PT-141 (Bremelanotide): Melanocortin Receptor Research Guide

PT-141, known by its INN Bremelanotide, is a synthetic cyclic heptapeptide and non-selective melanocortin receptor agonist. It is the active carboxyl-terminal metabolite of Melanotan II (MT-II), generated in vivo through enzymatic removal of the C-terminal amide group. PT-141 activates all melanocortin receptor subtypes (MC1R, MC3R, MC4R, MC5R) but has minimal MSH-type tanning activity compared to the parent compound MT-II.

Its molecular weight is approximately 1.0 kDa. The cyclic structure confers greater metabolic stability than linear melanocortin peptides, making it a useful tool in receptor pharmacology research.

The melanocortin system comprises five G-protein-coupled receptors (MC1R through MC5R), each with distinct tissue distribution and physiological roles:

• MC1R — predominantly expressed in melanocytes; regulates skin pigmentation and UV response
• MC2R — expressed in adrenal gland; mediates ACTH-stimulated cortisol production (not activated by PT-141)
• MC3R — expressed in brain and peripheral tissues; involved in energy homeostasis and autonomic function
• MC4R — widely expressed in the CNS; central regulator of appetite, energy expenditure, and autonomic signalling
• MC5R — expressed in exocrine glands and peripheral tissues; less well characterised

PT-141's research interest focuses primarily on MC3R and MC4R due to their roles in CNS-mediated physiology.

MC4R in the hypothalamus and brainstem is a well-established regulator of energy homeostasis, appetite suppression, and autonomic outflow. Research using MC4R agonists including PT-141 has investigated its effects on feeding behaviour, sympathetic tone, and metabolic rate in rodent models.

MC3R research with PT-141 has examined its role in energy sensing and the regulation of glucocorticoid responses to stress. The combination of MC3R/MC4R agonism in a single compound makes PT-141 a useful pharmacological tool for studying the overlapping and distinct functions of these receptor subtypes.

PT-141 and Melanotan II (MT-II) share structural similarities but have key differences relevant to research design:

• Receptor selectivity — MT-II has higher potency at MC1R (tanning) relative to PT-141; PT-141 shows relatively greater selectivity for CNS receptors in comparative studies
• Pigmentation activity — MT-II produces significant melanogenesis in animal studies; PT-141's effects on pigmentation are substantially reduced, making it preferable for CNS-focused research where pigmentation is a confounding variable
• Metabolic relationship — PT-141 is the in vivo metabolite of MT-II, meaning MT-II studies may be partly mediated by PT-141 formation; using PT-141 directly removes this confound

RetaLABS PT-141 10mg is supplied as lyophilised powder. Reconstitute with bacteriostatic water and store at 2–8°C for up to 4 weeks. Keep lyophilised vials at −20°C. See the Peptide Reconstitution Guide for full protocol notes. COAs available on request. For laboratory research use only.