MT-2 vs PT-141: Melanotan II and bremelanotide compared

The short version

MT-2 and PT-141 are nearly the same molecule. Both are cyclic seven-residue analogues of α-melanocyte-stimulating hormone designed at the University of Arizona, and both are agonists at several of the five melanocortin receptors. The only structural difference is the C-terminus: MT-2 ends in an amide, PT-141 in a free acid. PT-141 was identified as a metabolite of MT-2 and taken through clinical development in its place, and it is now licensed in the United States as bremelanotide. MT-2 has never been licensed anywhere and is the subject of long-standing MHRA warnings about its sale as a "tanning injection".

Both are supplied by BuyUK Peptides as research chemicals for in-vitro laboratory use only. Nothing on this page is guidance for any other use.

Structure

The design work behind the shared scaffold was published by Al-Obeidi, Hadley and Hruby, who used a lactam bridge and a D-phenylalanine to produce cyclic melanotropins far more potent and longer-lived than the native hormone [1]. The norleucine in place of methionine removes the oxidation weak point of α-MSH.

Receptor pharmacology

The melanocortin receptors are five Gs-coupled receptors. MC1R controls pigmentation in melanocytes; MC2R is the ACTH receptor in the adrenal; MC3R and MC4R are expressed mainly in the brain, where they regulate energy balance and, as the clinical work showed, sexual behaviour; MC5R is found in exocrine glands. MT-2 is a potent, non-selective agonist at MC1R, MC3R, MC4R and MC5R, which is the reason the original tanning programme also produced reports of appetite suppression and spontaneous erections [2].

PT-141 shares the scaffold and much of the receptor profile. It was developed for its central action at MC3R and MC4R [3], and its behavioural pharmacology was characterised in female rats by Pfaus and colleagues [4]. It is not fully selective: activity at MC1R persists, and the licensed product's label reports focal hyperpigmentation in some patients. For in-vitro work, neither is a selective probe for a single receptor; receptor identity has to be established with selective antagonists, knock-down or single-receptor expression systems.

From tanning agent to licensed medicine

MT-2 was developed in the 1990s as a sunless tanning agent. A pilot phase 1 study in healthy men reported tanning together with nausea, flushing and spontaneous erections [5], and later small studies looked at erectile function directly [6]. The clinical rights passed to Palatin Technologies, who identified the free-acid metabolite, named it PT-141, and developed it instead [3]. After a long programme, first as a nasal spray for erectile dysfunction and then as a subcutaneous product for hypoactive sexual desire disorder in premenopausal women, it was approved by the US FDA in 2019 [7].

UK regulatory position

Neither compound holds a UK marketing authorisation, and neither is a controlled drug. The MHRA has stated publicly since 2008 that products sold as Melanotan "tanning injections" are unlicensed medicines and has taken enforcement action against such sales [8]; the public-health literature from Liverpool documented that market [9]. The legal distinction rests on how a product is presented and supplied. Both compounds are sold here strictly as research chemicals for in-vitro laboratory use under the Terms of Sale, with no claim of any effect in people; our guide to the UK rules sets out why that matters.

Handling at the bench

The two handle identically. Both are supplied lyophilised and keep for years at −20 °C or for months at 2 to 8 °C sealed, protected from light. The tryptophan residue is the light-sensitive point. Both dissolve readily in water or bacteriostatic water to a clear solution; keep solutions cold and dark, and aliquot and freeze for storage beyond a few weeks. Choosing a reconstitution solvent covers the details.

Telling them apart on the certificate

This is the one place where the near-identity of the two matters. The molecular weights differ by about one dalton, 1,024.2 against 1,025.2, because an amide (–CONH2) has been replaced by an acid (–COOH). A low-resolution mass reading can blur that distinction, especially if the certificate quotes only a doubly charged ion, where the difference shrinks to half a mass unit (m/z 513.1 against 513.6). A sound certificate quotes the monoisotopic or deconvoluted mass to at least one decimal place, and ideally shows the two compounds' different retention times on HPLC: the free acid is slightly more polar and elutes earlier under the usual acidic gradient. RP-HPLC purity should be 98 per cent or above.

Which to choose

For melanocortin-receptor work that needs the broad-spectrum reference agonist with the longest literature, MT-2 is the standard tool. For work aligned with the clinical compound, or where a licensed reference standard and published analytical methods are useful, PT-141 is the better choice. Full accounts are in the monographs for MT-2 and PT-141.

References

1. Al-Obeidi F, Hadley ME, Pettitt BM, Hruby VJ. Design of a new class of superpotent cyclic α-melanotropins based on quenched dynamic simulations. Journal of the American Chemical Society. 1989;111(9):3413–3416. doi:10.1021/ja00191a044.
2. Hruby VJ, Lu D, Sharma SD, et al. Cyclic lactam α-melanotropin analogues of Ac-Nle4-cyclo[Asp5,D-Phe7,Lys10]-α-melanocyte-stimulating hormone-(4-10)-NH2 with bulky aromatic amino acids at position 7 show high antagonist potency and selectivity at specific melanocortin receptors. Journal of Medicinal Chemistry. 1995;38(18):3454–3461. doi:10.1021/jm00018a005.
3. Diamond LE, Earle DC, Rosen RC, Willett MS, Molinoff PB. 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. International Journal of Impotence Research. 2004;16(1):51–59. doi:10.1038/sj.ijir.3901139.
4. Pfaus JG, Shadiack A, Van Soest T, Tse M, Molinoff P. Selective facilitation of sexual solicitation in the female rat by a melanocortin receptor agonist. Proceedings of the National Academy of Sciences. 2004;101(27):10201–10204. doi:10.1073/pnas.0400491101.
5. Dorr RT, Lines R, Levine N, et al. Evaluation of Melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sciences. 1996;58(20):1777–1784. doi:10.1016/0024-3205(96)00160-9.
6. Wessells H, Gralnek D, Dorr R, Hruby VJ, Hadley ME, Levine N. Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction. Urology. 2000;56(4):641–646. doi:10.1016/S0090-4295(00)00680-4.
7. Dhillon S, Keam SJ. Bremelanotide: first approval. Drugs. 2019;79(14):1599–1606. doi:10.1007/s40265-019-01187-w.
8. Cancer Research UK. Melanotan injections are illegal and possibly unsafe. Science blog, 28 January 2009, reporting the MHRA warning and enforcement letters. news.cancerresearchuk.org.
9. Breindahl T, Evans-Brown M, Hindersson P, et al. Identification and characterization by LC-UV-MS/MS of melanotan II skin-tanning products sold illegally on the Internet. Drug Testing and Analysis. 2015;7(2):164–172. doi:10.1002/dta.1655.

This monograph summarises the published literature for laboratory researchers. It is not medical advice, and nothing on this site is for human or veterinary use.