Melanotan 2 spray

Product status information

Chemical reagent intended exclusively for laboratory tests (Research Use Only). It is not a medicinal product, dietary supplement or food. It is not intended for use on humans or animals. Sales only to registered research units and laboratories.

Melanotan II (MT-II) comes from a photoprotection program – not from a laboratory looking for a “natural spray tan.” The team of Mac Hadley and Victor Hruby at the University of Arizona designed this molecule in the 1980s with a clear goal: to pharmacologically increase endogenous skin pigmentation so as to reduce the dose of UV radiation needed to protect against skin cancer. Cyclization and replacement of two amino acid residues in the α-MSH sequence gave a metabolically stable analogue that was many times stronger than the parent hormone.

Thirty years later, MT-II is still not registered as a drug – the only registered derivative of the melanocortin pathway remains PT-141 (Bremelanotide, Vyleesi®), a later modification with greater selectivity for the MC4R receptor. This reagent from the line Endogenic is delivered as kit for self-preparation of nasal spray: vial with MT-II lyophilisate (10 mg), bacteriostatic water for reconstitution and a glass atomizer with a dosing pump. This is not a ready-to-use solution: the researcher first reconstitutes the lyophilized product with the included water and then fills the atomizer, preparing the solution for intranasal administration.

This format refers to intranasal administration of peptides – a route in which melanocortin peptide is absorbed through the nasal mucosa into the systemic circulation, with partial nose-to-brain transport along the olfactory and trigeminal nerves. This makes it one of peptides spray in the catalog in which the nasal route is included in the kit format itself.

Because the researcher reconstitutes the lyophilisate himself and selects the volume of water, he determines the working concentration of the solution according to the protocol – unlike a ready-made multi-dose applicator. Purity verified by HPLC ≥98%, identity confirmed by mass spectrometry, COA available for each batch.

Regulatory status

Melanotan II is not registered as a medicine in the EU, USA or anywhere in the world. University of Arizona clinical development program abandoned; the only registered derivative of the melanocortin pathway remains PT-141 (Bremelanotide). The FDA issued Warning Letters to sellers of MT-II in 2007, and the UK MHRA issued a consumer alert in 2008. Marketing a product as a “tan peptide”, “spray self-tanner”, “libido enhancer” or “erection aid” is inconsistent with the Research Use Only framework.

The melanocortin system is one of the most widely branched signaling pathways in mammals – one family of peptides (melanocortins) and five receptors (MC1R–MC5R) that control processes as diverse as skin pigmentation, appetite, inflammation, libido, and sebaceous gland secretion. The common denominator is their origin: all melanocortins (α-MSH, β-MSH, γ-MSH and ACTH) are formed from one protein precursor – proopiomelanocortin (POMC) — through enzymatic post-translational cleavage. α-MSH (melanocyte stimulating hormone) is the best characterized melanocortin.

It is a thirteen-amino-acid peptide that binds to melanocortin receptors and triggers a G-protein-dependent signaling cascade – mainly the cAMP/PKA pathway.

However, the research problem with native α-MSH is prosaic: the molecule is quickly degraded in the body (half-life measured in minutes), which makes it of little use as a tool for studying long-term modulation of the melanocortin pathway. This is where the MT-II comes into play. The Arizona team solved the stability problem by two modifications of the α-MSH sequence and cyclization of the peptide chain:

• Met⁴ → Nle⁴ replacement (norleucine) – removes the oxidation-sensitive sulfur atom of methionine, increasing chemical stability
• L-Phe⁷ → D-Phe⁷ replacement — inversion of the spatial configuration of the phenylalanine residue increases resistance to proteolysis and receptor affinity
• Cyclization via a lactam bridge (Asp–Lys) — stiffens the structure and stabilizes the active conformation

Effect: an analogue many times stronger than α-MSH, resistant to enzymatic degradation, with an extended period of activity. This makes MT-II a model ligand for studying pharmacology everyone melanocortin receptors – its non-selectivity, problematic from a therapeutic perspective, is an advantage in mechanistic studies of the MCR family as a whole.

Chemically, MT-II is a cyclic heptapeptide, an α-MSH analogue with a modified and stiffened core sequence. In this kit, it is supplied as a lyophilized product in a vial along with bacteriostatic water and a glass atomizer, from which the researcher prepares a solution for intranasal administration after reconstitution.

• Common name: Melanotan II, MT-II, MT2
• Chemical name: [Nle⁴,D-Phe⁷]-α-MSH(4-10) analog, cyclic via lactam bridge
• Synonyms: Melanotan 2, MT-II, melanotan ii
• CAS number: 121062-08-6
• Sequence: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂
• Molecular formula: C₅₀H₆₉N₁₅O₉
• Molar mass: 1024.18 g/mol
• Chemical class: cyclic heptapeptide, melanocortin analogue; full agonist (pan-agonist) of MC1R–MC5R receptors
• Supplied form: set – vial with MT-II lyophilisate (10 mg of active substance) + bacteriostatic water for reconstitution + glass nasal atomizer (for self-preparation of the solution); pharmaceutical grade ≥98% HPLC
• Line: Endogenic

Origin: MT-II was synthesized in the 1980s at the University of Arizona by the team of Mac E. Hadley and Victor J. Hruby as part of a research program on photoprotection and skin cancer prevention. The research hypothesis was that pharmacologically increasing endogenous pigmentation (eumelanin) would reduce UV-induced DNA damage and reduce the risk of skin cancer.

The molecule entered early Phase I studies (Dorr et al. 1996; Hadley & Hruby 1993), where its melanogenic activity in humans was confirmed, but also had two unexpected effects: induced erections and nausea. PT-141 (Bremelanotide) was then developed as a selective derivative of MC4R and ultimately approved by the FDA (2019, Vyleesi®). However, the MT-II program has not been registered.

MT-II works as full agonist of all five melanocortin receptors. MCR receptors are a class A of G protein-coupled receptors (GPCRs) – their activation increases intracellular cAMP concentration through adenylate cyclase and triggers the PKA pathway. Where a given receptor is located determines the observed phenotype. It is this broad, nonselective activation that distinguishes MT-II from selective ligands and explains its complex profile observed in the literature. Per receptor profile (observed in research models and early clinical literature):

1. MC1R (skin melanocytes) → melanogenesis. Activation of MC1R on melanocytes triggers the cAMP/PKA/MITF pathway, which increases the expression of tyrosinase – an enzyme that limits the rate of melanin synthesis. Net effect: shifting synthesis towards eumelanins (dark, photoprotective pigment) and increase in skin pigmentation. This was the original design goal of the MT-II (Dorr et al. 1996; Ugwu et al. 1997). The MC1R receptor in the skin is of systemic importance – it works regardless of the route of administration, because it is enough for the peptide to reach the systemic circulation.
2. MC4R (central nervous system) → appetite, erection, libido. MC4R in the hypothalamus and other CNS regions participates in the regulation of energy balance (appetite suppression) and in the central modulation of sexual functions. MC4R activation is associated with induced erections independent of the vascular stimulus (Wessells et al. 2000) and with a central effect on libido – it was this pathway that became the basis for the development of the selective PT-141.
3. MC3R (CNS, peripheral tissues) → energy balance. MC3R interacts with MC4R in the regulation of energy homeostasis and energy expenditure; its role is complementary to MC4R, although less thoroughly characterized.
4. MC2R (adrenal cortex) → ACTH pathway. MC2R is a receptor specific for ACTH (adrenal steroidogenesis). MT-II binds to MC2R weaker than to other receptors, but in the context of pan-agonism this pathway remains the subject of selectivity analysis.
5. MC5R (exocrine glands) → sebaceous and exocrine secretion. MC5R participates in the regulation of sebaceous and other exocrine glands; in animal models, its activation affects the production of sebum and pheromones.

Pharmacokinetic profile (based on early literature and models):

• Metabolic stability much higher than native α-MSH (effect of cyclization and Nle⁴/D-Phe⁷ substitutions)
• Plasma half-life in humans: on the order of several hours (partial data from Phase I studies; Ugwu et al. 1997)
• Absorption after parenteral administration is good; oral bioavailability is negligible (the peptide is digested in the gastrointestinal tract)
• Metabolism: proteolytic; elimination mainly renal

The intranasal administration format for which this kit is prepared refers to the intranasal administration of regulatory peptides. The molecular logic of this pathway has been well described in peptide neuropharmacology, although for MT-II itself it requires a fair distinction from the parenteral administration that dominates the literature. Melanocortin peptide administered intranasally can be absorbed via two parallel routes:

• Systemic absorption through the nasal mucosa — the richly vascularized mucosa of the nasal cavity allows the peptide to enter the general circulation, bypassing the digestive tract. For MT-II, this is an important pathway because the main effect observed in the literature – pigmentation by MC1R in the skin – is a result of system: depends on circulating peptide concentration, not on delivery to the brain.
• Partial nose-to-brain transport — a peptide applied to the olfactory epithelium in the upper part of the nasal cavity can be transported along the olfactory nerves to the olfactory bulb and along the trigeminal nerve endings to the brainstem, partially bypassing the blood-brain barrier. This route is important for central receptors (MC4R, MC3R in the CNS).

SCIENTIFIC PERSPECTIVE

The intranasal bioavailability of MT-II requires independent verification. Most documented pharmacokinetic data on MT-II and the related Melanotan-I are from parenteral (Ugwu et al. 1997), not intranasal, administration. Melanocortins act primarily systemically — the pigmentation effect (MC1R in the skin) depends on the concentration of the peptide in the general circulation, to which the intranasally administered peptide reaches through absorption through the nasal mucosa.

The nose-to-brain component is secondary for melanocortins in relation to their peripheral-systemic profile. In the research protocol, this means that intranasal MT-II pharmacokinetics—fraction absorbed, kinetics, and reproducibility—should be characterized separately and not assumed by analogy to parenteral administration or to peptides with a purely central profile (like Selank).

Three points require clear separation.

Firstly – dermatological and oncological risk. described in the literature rare cases changes in atypical moles and melanocytic lesions in people exposed to MT-II (Reid et al. 2013 and subsequent case reports). The mechanistic hypothesis links this to MC1R stimulation and melanocyte proliferation/activation. At the evidentiary level, this remains a safety signal from case reports, rather than a proven cause-and-effect relationship in the population – a factor that makes MT-II compound with a real risk profile.

“Pigmentation by MC1R” in the context of this description means a melanogenic observation in models and early literature, not a guarantee of a safe cosmetic effect in humans.

Secondly – MT-II is not identical to PT-141. MT-II is a full pan-agonist of MC1R–MC5R; PT-141 (Bremelanotide) is a selective derivative targeting MC4R. The chemical difference (amide –NH₂ vs. carboxyl –COOH at the C-terminus) translates into fundamentally different selectivity profiles. Confusing the two compounds in a research protocol is a methodological error – they are two different tools for two different research questions. The selectivity comparison is described for the reagent PT-141 10mg — selective derivative of MC4R.

Thirdly, intranasal administration has a different bioavailability than injection. The predominant pharmacokinetic data on MT-II come from parenteral administration, where absorption is almost complete.

Intranasal administration offers a different, partial absorption profile – the fraction of peptide entering the circulation depends on the formulation, spray volume and mucosal condition. Working concentrations in the intranasal protocol are not 1:1 convertible to concentrations from parenteral studies. Related formats – Melanotan 2 10mg (lyophilized vial only, without water and atomizer) and Melanotan 2 PEN (ready-made multi-dose applicator, factory solution) – require separate bioavailability characterization in a given research protocol.

MT-II is used in research as a model pan-agonist of melanocortin receptors – a tool for studying the entire MCR system and a reference point in comparative studies of ligand selectivity. The nasal spray kit format adds a dimension to the study of the nasal route. Receptor affinity, cAMP activation kinetics and functional selectivity are examined in in vitro models (human and mouse melanocyte lines, recombinant MC1R–MC5R receptor expression systems, HEK293 cell cultures transfected with MCR). In vivo models (rodents, the historical Anolis lizard model for the melanogenesis test) assess the pigmentation and metabolic response. Specific research directions include:

• Pharmacology of melanogenesis and photoprotection — MC1R/cAMP/MITF/tyrosinase pathway; evaluation of eumelanin synthesis as a model for the prevention of UV damage (original context from Arizona)
• Comparative studies of receptor selectivity — MT-II (pan-agonist) vs PT-141 (selective MC4R) vs selective MC1R ligands; mapping of functional profiles
• MC4R central modulation — energy balance, appetite suppression, central pathways of sexual function in rodent models
• Melanocortin signaling in exocrine glands — role of MC5R in the regulation of sebaceous glands (animal models)
• Characterization of intranasal administration — comparative pharmacokinetics of absorption through the nasal mucosa versus parenteral administration; assessment of the systemic fraction and nose-to-brain component for melanocortin peptide
• Melanocytic risk studies — the impact of chronic MC1R activation on the proliferation and phenotype of melanocytes (dermatopharmacological and oncological context)

Melanotan II (MT-II) is a cyclic heptapeptide, an α-MSH analogue designed in the 1980s at the University of Arizona (Hadley, Hruby) in the photoprotection research program. Thanks to cyclization and Nle⁴ and D-Phe⁷ replacements, it is metabolically stable and acts as full pan-agonist of MC1R–MC5R receptors — which distinguishes it from PT-141 (Bremelanotide), a selective derivative of MC4R differing in the C-terminus (amide instead of carboxyl).

In models and early Phase I literature, MT-II demonstrated melanogenic activity (MC1R), induced erections and central effects on libido (MC4R), and nausea; Rare cases of changes in atypical moles have also been described – a real safety signal.

Form: kit for self-preparation of nasal spray – vial with lyophilisate (10 mg), bacteriostatic water for reconstitution and glass atomizer; the researcher reconstitutes the lyophilisate and fills the atomizer, Endogenic line. Melanocortin peptide administered intranasally is absorbed through the nasal mucosa into the general circulation (systemic action, including pigmentation by MC1R) with partial nose-to-brain transport – however, the intranasal bioavailability of MT-II requires separate verification and is not recalculated from the concentrations resulting from parenteral administration. HPLC purity ≥98%, MS confirmation (Q-TOF), COA for each batch.

Regulatory Status – Research Use Only; no registration in any jurisdiction; WADA status: not listed (as of 2024).

1. Dorr RT, Lines R, Levine N, Brooks C, Xiang L, Hruby VJ, et al. (1996). Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. PubMed
2. Hadley ME, Sharma SD, Hruby VJ, Levine N (1993). Melanotropic peptides for therapeutic and cosmetic tanning of the skin. PubMed
3. Wessells H, Levine N, Hadley ME, Dorr R, Hruby VJ (2000). Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II. PubMed
4. Ugwu SO, Blanchard J, Dorr RT, Levine N, Brooks C, Hadley ME, et al. (1997). Skin pigmentation and pharmacokinetics of melanotan-I in humans. PubMed
5. Reid C, Fitzgerald T, Fabre A, Kirby B (2013). Atypical melanocytic naevi following melanotan injection. PubMed