PT-141, also known by its generic name bremelanotide, is a cyclic seven-residue peptide built on the active core of α-melanocyte-stimulating hormone (α-MSH). It binds several melanocortin receptors, and its activity in the central nervous system made it a reference ligand for studying how brain melanocortin pathways connect to motivated behavior in rodents.
It is also one of the few research peptides with a regulatory history that ended in an approved drug product. This overview covers its origin in the melanotan program, its chemistry, the receptor pharmacology, the main preclinical models, and what the published research leaves open.
At a glance
- Class: Synthetic cyclic heptapeptide; α-MSH analog and melanocortin receptor agonist
- Origin: Derived from melanotan II; developed by Palatin Technologies (Molinoff et al., 2003)
- Structure: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH, lactam bridge between Asp and Lys side chains; C50H68N14O10; 1025.2 g/mol; CAS 189691-06-3
- Main research areas: melanocortin receptor pharmacology, hypothalamic MC4R circuits, rodent behavioral neuroscience, cardiovascular effects of melanocortin agonism
- Regulatory status: Bremelanotide is the active ingredient of an FDA-approved drug product (2019, specific indication); the material sold here is a research reagent
Structure and origin
α-MSH is a 13-residue linear peptide that is broken down quickly by proteases. In the 1980s and 1990s, researchers at the University of Arizona designed more stable analogs, and one of these, melanotan II, condensed the hormone’s active region into a small ring. PT-141 came out of that same chemistry. It shares melanotan II’s ring and N-terminal residues but ends in a free carboxylic acid instead of an amide, a single change that gives it a distinct identity and CAS number.
Several design features make the molecule stable and potent. The lactam bridge between the side chains of aspartic acid and lysine locks the peptide into a ring and shields it from many proteases. Norleucine at the N-terminus replaces the oxidation-prone methionine of α-MSH. D-phenylalanine in place of L-phenylalanine within the His-Phe-Arg-Trp core increases receptor potency, a substitution known from earlier α-MSH analog work. Palatin Technologies advanced the compound into development and described its pharmacology as a melanocortin agonist acting in the central nervous system (Molinoff et al., 2003).
Mechanism: what the research shows
The melanocortin system includes five G protein-coupled receptors, MC1R through MC5R. MC2R responds only to ACTH; the others respond to MSH peptides. The His-D-Phe-Arg-Trp sequence in PT-141 lets it bind several of these subtypes, so it is not a selective tool for any single receptor. Research interest centers on MC4R and MC3R, which are expressed in the hypothalamus and other brain regions and signal mainly through Gs and cAMP.
Rodent work placed the relevant action in the brain rather than in peripheral tissue. A review of preclinical CNS data describes effects linked to hypothalamic regions, including the medial preoptic area, and to downstream dopamine signaling (Pfaus et al., 2007). That central site of action is what distinguished PT-141 from compounds acting on peripheral blood flow.
Key areas of study
Receptor pharmacology
Binding and cAMP assays across melanocortin receptor subtypes, often run side by side with α-MSH and melanotan II, are the starting point for most PT-141 research. Structure-activity comparisons within this family helped define which ring and terminal modifications change receptor potency and selectivity (Molinoff et al., 2003).
Rodent behavioral neuroscience
In a study in hormone-primed female rats, PT-141 increased specific appetitive behaviors, such as solicitations, in a paced-mating paradigm, while consummatory measures such as lordosis were not changed (Pfaus et al., 2004). The ability to separate these behavior types made the compound useful for mapping where melanocortin signaling acts in the reward and motivation circuitry (Pfaus et al., 2007).
Central melanocortin circuits
Researchers also use PT-141 to study how MC4R signaling in hypothalamic nuclei, including the paraventricular nucleus, links to dopaminergic and other neurotransmitter systems. These experiments typically pair region-specific approaches in rodents with neurochemical or behavioral readouts (Pfaus et al., 2007).
Cardiovascular effects
Melanocortin agonists can affect blood pressure and heart rate, and this receptor-family feature followed PT-141 through its development. Transient blood pressure increases were a safety focus in clinical studies, and they are discussed in regulatory summaries of the compound (Dhillon and Keam, 2019).
What the evidence does not show
- Rodent behavioral findings are model-specific and do not translate directly to human physiology.
- PT-141 binds several melanocortin receptor subtypes, so effects in vivo cannot be attributed to a single receptor without additional tools such as selective antagonists or knockout models.
- The approved drug product covers one narrowly defined indication, studied with a specific formulation. That approval does not extend to research material or to any other use.
- Earlier clinical work on other formulations, such as an intranasal version evaluated in men (Diamond et al., 2004), did not lead to an approved product.
Regulatory status
Bremelanotide is the active ingredient of Vyleesi, a prescription drug product approved by the FDA in June 2019 for a specific indication: acquired, generalized hypoactive sexual desire disorder in premenopausal women (Dhillon and Keam, 2019). The PT-141 sold by Rogue Compounds is a research reagent, not an approved drug product, and is not for human use.
Handling and storage in the lab
Lyophilized PT-141 should be kept sealed and refrigerated at 2–8°C (36–46°F), protected from light.
Sourcing and documentation
PT-141 is made in small batches for Rogue Compounds. Every vial carries a batch number and a QR code that opens the independent U.S. testing lab’s own report for that batch, and the same batch COA is on the product page and in the COA Library.
View PT-141 on Rogue Compounds
References
- Molinoff PB, et al. PT-141: a melanocortin agonist for the treatment of sexual dysfunction. Ann N Y Acad Sci. 2003;994:96-102. PMID 12851303
- Pfaus JG, et al. Selective facilitation of sexual solicitation in the female rat by a melanocortin receptor agonist. Proc Natl Acad Sci USA. 2004;101(27):10201-10204. PMID 15226502
- Pfaus J, Giuliano F, Gelez H. Bremelanotide: an overview of preclinical CNS effects on female sexual function. J Sex Med. 2007;4 Suppl 4. PMID 17958619
- Diamond LE, et al. Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction. Int J Impot Res. 2004;16(1):51-59. PMID 14963471
- Dhillon S, Keam SJ. Bremelanotide: first approval. Drugs. 2019;79(14):1599-1606. PMID 31429064
Research use only. Rogue Compounds products are sold strictly for laboratory research. They are not for human or veterinary use, and nothing in this article is medical advice. The studies cited here describe published research, not this product or any use of it.