PT-141 is a research peptide that has garnered interest due to its unique structure and potential interactions with specific types of cells and tissues. More specifically, PT-141 is a heptapeptide made of seven amino acids and has the following sequence: Ac-Nle-Asp-His-D-Phe-Arg-Trp-Lys-OH.(1) Here, ‘Ac’ stands for an acetyl group, and ‘OH’ represents an hydroxyl group at the C-terminal end. Structurally, PT-141 is a cyclic peptide which means it features a ring-like formation that is posited as crucial to its potential activity. This cyclic structure is apparently formed via a lactam bridge (a chemical bond that connects two amino acids in the sequence) between the side chain of aspartic acid (Asp) at second position and the ε-amino group of lysine (Lys) at seventh position. This lactam bond is considered a key stabilizing factor in the peptide’s conformation. Researchers should continue reading to discover in depth information on what PT-141 is, how it works and what are its main research applications.


What Is PT-141 Peptide?

The amino acid sequence of PT-141 is derived from the hormone alpha-MSH (alpha melanocyte-stimulating hormone) and includes modifications that distinguish it from naturally occurring peptides.(2) The sequence of PT-141 peptide is crafted to potentially interact with melanocortin receptors, which are found in various tissues throughout the body. PT-141 is also considered to be a by-product of the metabolism of another synthetic analog called Melanotan II. PT-141 and Melanotan II retain only four of the original amino acids of alpha-MSH, more specifically the His-Phe-Arg-Trp sequence, which makes up the amino acids from 6th to 9th position in alpha-MSH. This appears to be sufficient to provide an observable activation of several types of melanocortin receptors. Moreover, Phe (L-phenylalanine) is replaced with D-Phe (D-phenylalanine) in PT-141 to further support the stability of this cyclic peptide.


How Does PT-141 Work?

PT-141’s potential is thought to be mediated through its interaction with the melanocortin receptors in various cells and tissues. For instance, in melanocytes – cells responsible for pigment production in the skin – PT-141 peptide might influence melanin synthesis. This interaction is posited to be a result of its structural affinity for melanocortin receptors, which are integral to the process of melanogenesis. Scientists have identified a total of five types of melanocortin receptors, each with its unique potential mechanisms and functionality.(3)(4) Here is a detailed breakdown of their location, potential function and importance: 

  • The melanocortin 1 receptor is primarily found in melanocytes, cells that are responsible for skin and hair pigmentation. It is posited that the melanocortin 1 receptor influences these aspects by potentially promoting melanin synthesis, the pigment responsible for coloration.
  • The melanocortin 2 receptor appears to be predominantly located in the adrenal cortex, a part of the adrenal gland. It is suggested that the melanocortin 2 receptor is involved in the production of cortisol, a hormone that plays a role in stress response among other functions.
  • The melanocortin 3 receptor is expressed in various tissues, including the brain and placenta. It is implicated, though not definitively proven, in regulating appetite and energy balance, suggesting a role in metabolic processes.
  • The melanocortin 4 receptor is located in the central nervous system, particularly in the hypothalamus. This receptor potentially influences sexual behavior and erectile function. Additionally, the melanocortin 4 receptor might have a role in energy homeostasis, which is crucial for maintaining the body’s energy balance.
  • The melanocortin 5 receptor is expressed in multiple tissues. Its exact physiological role remains relatively undefined. However, it is believed, though not confirmed, to be involved in exocrine functions, which are related to the secretion of substances in the body.

PT-141 peptide is posited to have affinity only towards the melanocortin 1, melanocortin 3, and melanocortin 4 receptors. More specifically, the researchers commented that PT-141 “has strong binding to MC receptors 1, 3 and 4, with a higher affinity for MC4R over MC3R. Application of PT-141 to HEK-293 cells expressing MC4R increases cAMP production, indicating that this compound, like MT-II, acts as an agonist(5)


Research Applications of PT-141 Peptide

Below we have outlined the most notable trials that outline the potential of PT-141 peptide in activating various melanocortin receptors, notably the melanocortin 1, melanocortin 3, and melanocortin 4 receptors, as well as the apparent research applications of these observations.

PT-141 Peptide and Melanocortin 1 Receptors

PT-141 peptide is typically researched for its apparent interactions with the melanocortin 3 and 4 receptors. Yet, the peptide also interacts actively with the melanocortin 1 receptors which play a crucial role in melanogenesis, the process of melanin synthesis in melanocytes.(6) The exact mechanism of PT-141’s action on melanocortin 1 receptors is not fully elucidated, but it is hypothesized to involve several steps at the cellular level. Melanocortin 1 receptors, a G protein-coupled receptor located on the surface of melanocytes, are suggested as key regulators in melanogenesis. When PT-141 peptide binds to melanocortin 1 receptors, it is suggested to have agonistic action that may trigger a conformational change in the receptor, activating the associated G protein. This activation potentially leads to the stimulation of adenylate cyclase, an enzyme that catalyzes the conversion of ATP to cyclic AMP (cAMP). The increase in cAMP levels is thought to activate protein kinase A (PKA). PKA, in turn, may phosphorylate specific proteins and transcription factors, such as the microphthalmia-associated transcription factor (MITF). Phosphorylated MITF is posited to translocate into the nucleus, where it potentially upregulates the transcription of genes encoding enzymes crucial for melanin synthesis, such as tyrosinase, tyrosinase-related protein 1 (TRP1), and tyrosinase-related protein 2 (TRP2). These enzymes are central to the melanin synthesis pathway. Tyrosinase, for instance, is hypothesized to catalyze the initial step in melanin synthesis, the hydroxylation of tyrosine to L-DOPA, and subsequently the oxidation of L-DOPA to dopaquinone. TRP1 and TRP2 may further modify these intermediates, leading to the production of eumelanin or pheomelanin, depending on the enzymatic pathways activated and the presence of certain cofactors. It is also postulated that PT-141’s interaction with melanocortin 1 receptors might influence other signaling pathways, possibly impacting melanocyte proliferation and differentiation, although these actions are not as well characterized.

PT-141 Peptide and Melanocortin 3 Receptors

Similar to melanocortin 1 receptor activation, PT-141 peptide is suggested to potentially activate the melanocortin 3 receptors which predominantly couples with G proteins, more specifically Gs to activate cAMP and PKA, potentially causing alterations in gene expression. That is posited, albeit the lower apparent affinity of PT-141 to melanocortin 3 receptors compared to melanocortin 1 and 4 receptors.(7) In addition to the Gs protein pathway, the melanocortin 3 receptor activation may engage other G protein subtypes, potentially leading to different intracellular signaling cascades. For instance, coupling with Gi protein might result in the inhibition of adenylyl cyclase, thereby reducing cAMP levels. This diversity in G protein coupling is posited to contribute to the multifaceted roles of melanocortin 3 receptors in cellular regulation. The potential activation of melanocortin 3 receptors from ligands such as PT-141 peptide and its apparent downstream signaling pathways may influence various cellular processes. These are posited to include modulation of energy balance, regulation of food intake, and possibly impacting inflammatory responses at a cellular level. The precise outcomes of melanocortin 3 receptor activation may vary depending on the cellular context, the specific ligand involved, and the intracellular signaling pathways engaged. Moreover, melanocortin 3 receptor activation may also influence other signaling mechanisms, such as the mitogen-activated protein kinase (MAPK) pathway. This pathway, which includes extracellular signal-regulated kinases (ERK1/2), may be activated independently or in conjunction with cAMP/PKA signaling, leading to further modulation of cellular responses. On a broader scale, the cellular responses elicited by melanocortin 3 receptor activation reflect the receptor’s potential in maintaining energy balance and metabolic regulation. The receptor’s potential to interact with multiple ligands and engage diverse signaling pathways may enable it to act as a critical regulator of these complex cellular processes.

PT-141 Peptide and Melanocortin 4 Receptors

The melanocortin 4 receptors appear to be the main target of interest for researchers investigating the actions of PT-141 peptide. The peptide appears to interact with the melanocortin 4 receptors within a crucial brain region known as the medial preoptic area (mPOA) where they appear to be more densely distributed. The mPOA plays a vital role in initiating and regulating sexual behaviors across various species. This interaction suggests that PT-141 peptide might specifically target areas in the brain that are essential for sexual arousal and behavior in various scientific models. Moreover, this interaction seems to stimulate dopamine terminals in the mPOA.(8) The researchers commented that the peptide “activates the mPOA and other hypothalamic and limbic regions of the brain involved in sexual behavior, and may work by activating dopamine terminals in the mPOA.” Dopamine is considered a hormone that plays a crucial role for pleasure and reward in the central nervous system. Its activation in the mPOA might be a key player in the way PT-141 influences sexual behavior, possibly by enhancing the feelings of pleasure and reward associated with sexual activity. Additionally, the action of PT-141 peptide appears to induce the expression of a gene product named Fos in several brain regions, notably the nucleus accumbens, mPOA, and ventral tegmental area. These areas are considered in scientific models related to processing rewards and motivational aspects of behavior, including sexual behavior. The nucleus accumbens, for example, is posited as another reward center in the central nervous system. The activation of Fos, an immediate-early gene product, is often seen as a marker of neuronal activity. This suggests that PT-141 peptide might be activating neural pathways associated with anticipation and enjoyment in sexual activity models. There also appears to be an increase in dopamine release specifically in the mPOA when PT-141 is administered. This again points to the potential action of PT-141 peptide in modulating sexual behavior, possibly by enhancing the reward and pleasure sensations specifically associated with sexual activity in test models. Further, the compound’s actions may not be limited to the brain. It is suggested that PT-141, along with the melanocortin systems, may influence both the central and peripheral nervous systems during exposure to sexual stimuli in scientific models. This implies a coordinated response, both mentally and physically, to sexual stimuli, enhancing the overall sexual experience in the laboratory models.(9) 



In conclusion, PT-141, a research peptide, exhibits intriguing potential in interacting with various melanocortin receptors, notably melanocortin 1, 3, and 4. Originating from alpha-MSH, its unique structural modifications present a distinct avenue for melanocortin system research. PT-141’s engagement with these receptors suggests its influence on a spectrum of cellular activities, ranging from melanogenesis in melanocytes to the possible modulation of energy balance and impact on sexual behavior in scientific studies. Furthermore, the potential to stimulate gene expression, such as Fos activation in brain areas linked to reward and motivation, offers insights into the neural pathways and molecular dynamics involved in complex behaviors and physiological activities. As a research tool, PT-141 is instrumental in enhancing the scientific comprehension of the melanocortin system, potentially revealing new regulatory mechanisms and interactions in cellular and systemic contexts.


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  2. Molinoff, P. B., Shadiack, A. M., Earle, D., Diamond, L. E., & Quon, C. Y. (2003). PT-141: a melanocortin agonist for the treatment of sexual dysfunction. Annals of the New York Academy of Sciences, 994, 96–102.
  3. Cai, M., & Hruby, V. J. (2016). The Melanocortin Receptor System: A Target for Multiple Degenerative Diseases. Current protein & peptide science, 17(5), 488–496.
  4. Ji, L. Q., Hong, Y., & Tao, Y. X. (2022). Melanocortin-5 Receptor: Pharmacology and Its Regulation of Energy Metabolism. International journal of molecular sciences, 23(15), 8727.
  5. King, S. H., Mayorov, A. V., Balse-Srinivasan, P., Hruby, V. J., Vanderah, T. W., & Wessells, H. (2007). Melanocortin receptors, melanotropic peptides and penile erection. Current topics in medicinal chemistry, 7(11), 1098–1106.
  6. Mun, Y., Kim, W., & Shin, D. (2023). Melanocortin 1 Receptor (MC1R): Pharmacological and Therapeutic Aspects. International journal of molecular sciences, 24(15), 12152.
  7. Yuan, X. C., & Tao, Y. X. (2022). Ligands for Melanocortin Receptors: Beyond Melanocyte-Stimulating Hormones and Adrenocorticotropin. Biomolecules, 12(10), 1407.
  8. Pfaus, J., Giuliano, F., & Gelez, H. (2007). Bremelanotide: an overview of preclinical CNS effects on female sexual function. The journal of sexual medicine, 4 Suppl 4, 269–279.
  9. Pfaus, J. G., Sadiq, A., Spana, C., & Clayton, A. H. (2022). The neurobiology of bremelanotide for the treatment of hypoactive sexual desire disorder in premenopausal women. CNS spectrums, 27(3), 281–289.
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