Melanotan 2 (MT-2, also written MT-II) and PT-141 (bremelanotide) are synthetic analogs of alpha-melanocyte-stimulating hormone (α-MSH) that act at melanocortin receptors. They are closely related in structure, but they have been used to answer different research questions. This page compares what the published literature says about each, so you can choose the right tool for a melanocortin study.
Both compounds are supplied by BioSim for laboratory research only. They are not for human or veterinary use, and nothing here is guidance on administration to people.
The Melanocortin System in Brief
The melanocortin system includes five G protein-coupled melanocortin receptors (MC1R to MC5R), peptide agonists derived from proopiomelanocortin (POMC), and the endogenous antagonists agouti and agouti-related protein. It regulates a wide range of functions, including pigmentation, adrenal steroid production, energy homeostasis and erectile responses (Cone, 2006). MC4R is a key node for energy balance: mice lacking MC4R develop maturity-onset obesity with hyperphagia, hyperinsulinemia and hyperglycemia (Huszar et al., 1997). For a general introduction to receptor activation, see our guide to peptide receptor signaling.
Melanotan 2: A Potent, Non-Selective Cyclic Agonist
Melanotan 2 (Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2) comes from a series of cyclic lactam analogs of α-MSH designed in the late 1980s using structure-activity data and molecular dynamics. These truncated α-MSH(4-10) analogs proved potent and long-acting in frog and lizard skin bioassays (Al-Obeidi et al., 1989). A later review describes MT-II as a cyclic, truncated, enzymatically resistant analog (Hadley & Dorr, 2006).
MT-II is best described as superpotent but non-selective. A study that systematically modified its backbone tested binding and activation at MC1R, MC3R, MC4R and MC5R and started from the premise that the parent peptide lacks subtype selectivity (Doedens et al., 2010). That breadth is useful when the aim is to study melanocortin signaling as a whole, but it means pigmentation (MC1R) and central effects (MC3R/MC4R) can occur together in the same experiment.
Published research uses MT-II across several areas:
- Pigmentation and skin biology: MC1R signaling, which the melanocortin system uses to control pigmentation (Cone, 2006).
- Feeding behavior: when microinjected into the nucleus accumbens of mice, MT-II decreased food consumption and the motivation to obtain food, without conditioned taste avoidance or changes in metabolic rate (Eliason et al., 2022).
- Central melanocortin pharmacology: as a reference agonist when testing new, more selective analogs (Doedens et al., 2010).
PT-141 (Bremelanotide): A Melanocortin Agonist for Sexual Behavior Research
PT-141 was developed as an analog of MT-II (Hadley & Dorr, 2006). It is described as an agonist at melanocortin receptors including MC3R and MC4R, which are expressed mainly in the central nervous system. In rats, systemic administration activated hypothalamic neurons, shown by increased c-Fos immunoreactivity (Molinoff et al., 2003). Central melanocortin receptors, with MC4R emerging as the main effector, are implicated in the control of erection, while the role of MC3R is less well understood (King et al., 2007).
PT-141 is the main research tool for studying melanocortin control of sexual motivation. In female rats, it selectively increased solicitational (appetitive) behaviors without affecting lordosis, pacing or other sexual behaviors, without generalized motor activation and without changing the perception of sexual reward (Pfaus et al., 2004). Follow-up work found the same effect after infusion directly into the lateral ventricles or the medial preoptic area, but not the ventromedial hypothalamus, and suggested a role for dopamine release in the medial preoptic area (Pfaus et al., 2007).
Bremelanotide is also an approved prescription medicine in the United States, where it is described as having high affinity for MC4R (Dhillon & Keam, 2019). The PT-141 sold by BioSim is a research reagent. It is not that medicine and is not for human use.
Key Research Comparison
| Property | Melanotan 2 | PT-141 |
|---|---|---|
| Origin | Cyclic lactam α-MSH(4-10) analog (Al-Obeidi et al., 1989) | Analog of MT-II (Hadley & Dorr, 2006) |
| Receptor profile in the literature | Superpotent, non-selective across MC1R, MC3R, MC4R and MC5R (Doedens et al., 2010) | Agonist at MC3R and MC4R (Molinoff et al., 2003); high MC4R affinity (Dhillon & Keam, 2019) |
| Pigmentation (MC1R) | A core research use | Not a primary focus of the published work; check in your own assay system |
| Feeding behavior | Reduced intake after nucleus accumbens microinjection in mice (Eliason et al., 2022) | Not a primary focus of the cited studies |
| Sexual behavior research | Historically used for erectile research (Hadley & Dorr, 2006) | Selective increase in appetitive behavior in female rats (Pfaus et al., 2004) |
| Regulatory status | Research chemical | Bremelanotide approved as a prescription medicine; BioSim’s PT-141 is a research reagent only |
Choosing the Right Tool for Melanocortin Research
Choose Melanotan 2 when you want broad melanocortin receptor activation, including pigmentation endpoints, or need a well-characterized reference agonist. Choose PT-141 when your study focuses on central melanocortin control of sexual behavior and you want to build on the rodent behavioral literature above. Do not assume either compound is fully selective. Confirm the receptor profile in your own system, ideally with selective antagonists or receptor-knockout controls. Because MC4R also controls energy balance, studies of either compound should monitor food intake and body weight as possible confounders. Our metabolic research overview covers other energy-balance tools, and our guide to neuropeptides in research covers central peptide signaling more broadly.
Every lot is third-party tested, with identity confirmed by mass spectrometry. To check a lot before use, see how to read a certificate of analysis.
References
- Al-Obeidi F, Castrucci AM, Hadley ME, et al. (1989). Potent and prolonged acting cyclic lactam analogues of alpha-melanotropin: design based on molecular dynamics. Journal of medicinal chemistry, 32(12), 2555-61. PMID: 2555512 · DOI: 10.1021/jm00132a010
- Cone RD (2006). Studies on the physiological functions of the melanocortin system. Endocrine reviews, 27(7), 736-49. PMID: 17077189 · DOI: 10.1210/er.2006-0034
- Dhillon S, Keam SJ (2019). Bremelanotide: First Approval. Drugs, 79(14), 1599-1606. PMID: 31429064 · DOI: 10.1007/s40265-019-01187-w
- Doedens L, Opperer F, Cai M, et al. (2010). Multiple N-methylation of MT-II backbone amide bonds leads to melanocortin receptor subtype hMC1R selectivity: pharmacological and conformational studies. Journal of the American Chemical Society, 132(23), 8115-28. PMID: 20496895 · DOI: 10.1021/ja101428m
- Eliason NL, Martin L, Low MJ, et al. (2022). Melanocortin receptor agonist melanotan-II microinjected in the nucleus accumbens decreases appetitive and consumptive responding for food. Neuropeptides, 96, 102289. PMID: 36155088 · DOI: 10.1016/j.npep.2022.102289
- Hadley ME, Dorr RT (2006). Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization. Peptides, 27(4), 921-30. PMID: 16412534 · DOI: 10.1016/j.peptides.2005.01.029
- Huszar D, Lynch CA, Fairchild-Huntress V, et al. (1997). Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell, 88(1), 131-41. PMID: 9019399 · DOI: 10.1016/s0092-8674(00)81865-6
- King SH, Mayorov AV, Balse-Srinivasan P, et al. (2007). Melanocortin receptors, melanotropic peptides and penile erection. Current topics in medicinal chemistry, 7(11), 1098-1106. PMID: 17584130
- Molinoff PB, Shadiack AM, Earle D, et al. (2003). PT-141: a melanocortin agonist for the treatment of sexual dysfunction. Annals of the New York Academy of Sciences, 994, 96-102. PMID: 12851303 · DOI: 10.1111/j.1749-6632.2003.tb03167.x
- Pfaus JG, Shadiack A, Van Soest T, et al. (2004). Selective facilitation of sexual solicitation in the female rat by a melanocortin receptor agonist. Proceedings of the National Academy of Sciences of the United States of America, 101(27), 10201-4. PMID: 15226502 · DOI: 10.1073/pnas.0400491101
- 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, 269-79. PMID: 17958619 · DOI: 10.1111/j.1743-6109.2007.00610.x
Research These Compounds: Melanotan 2 10mg and PT-141 10mg available from BioSim Peptides — 99%+ purity by HPLC, lyophilized; available certificates are published on our COA page.
