If you have been reading about melanocortin receptor and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.
Updated 2025-09-13. Numbers and descriptions here follow the published literature rather than marketing material.
Melanotan-2, also written Melanotan II, is a synthetic cyclic heptapeptide designed as an analogue of alpha-melanocyte-stimulating hormone. Its sequence is Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, and the lactam bridge between the aspartate and lysine side chains constrains the peptide into a ring. This structural change increases receptor affinity and metabolic stability relative to the native hormone. The compound was created in the 1980s as a research tool for studying pigmentation biology.
Melanocytes are the pigment-producing cells of the skin, and they carry melanocortin-1 receptors on their surface. When the receptor is activated, cyclic adenosine monophosphate rises inside the cell and raises the activity of enzymes such as tyrosinase, which increases melanin output. Melanotan-2 binds melanocortin-1 receptors in vitro and in animal models, and this binding is generally described as the basis for the tanning effect. Other receptors account for different effects: melanocortin-4 receptors contribute to appetite and erectile signalling, while melanocortin-3 and melanocortin-5 receptors contribute to energy balance and exocrine function.
Melanotan II binds several melanocortin receptor subtypes rather than a single target. MC1R on melanocytes drives melanin synthesis, while MC3R and MC4R participate in energy balance, appetite, and sexual response pathways. This lack of selectivity explains why reported effects extend beyond skin darkening. Substitutions at positions four and seven, including norleucine and D-phenylalanine, increase potency and resistance to peptidases. Understanding which receptor mediates which effect remains an active area of investigation.
Published human data come mostly from small, short studies rather than large controlled trials. Reported outcomes include increased skin pigmentation and, in some reports, effects on appetite and libido, but sample sizes are small and follow-up is limited. Whether long-term use produces durable pigment changes or adverse effects is not established. Because products sold outside pharmacies are not standardized, the actual content of any given vial is often unknown. Independent testing of such material is uncommon.
Melanotan II is a synthetic cyclic heptapeptide analog derived from the core sequence of alpha-melanocyte-stimulating hormone. Researchers at the University of Arizona synthesized it during the 1980s while studying pigmentation and appetite signaling. The compound is not an approved medicine in any major jurisdiction and appears mainly in laboratory and research-chemical settings. Its structure incorporates a lactam bridge between side chains, which constrains the ring and slows enzymatic breakdown relative to the natural hormone.
| Property | Value | Notes |
|---|---|---|
| Compound class | Synthetic cyclic heptapeptide | Alpha-MSH analogue containing a D-phenylalanine residue |
| Molecular formula | C50H69N15O9 | Average molecular mass approximately 1024.2 g/mol |
| Appearance | White to off-white lyophilised powder | Normally supplied as a freeze-dried solid in a sealed vial |
| Solubility | Freely soluble in water and polar solvents | Dissolves readily in aqueous buffers and in alcohol-water mixtures |
| Receptor targets | MC1R, MC3R, MC4R, MC5R | Acts as a non-selective melanocortin receptor agonist |
No regulatory authority has approved melanotan-2 for human use, and several countries classify it as a prescription-only or controlled substance, which restricts lawful supply. Material sold online is generally labelled as a research chemical and is not required to meet pharmaceutical standards of identity or purity. Published human data consist mainly of small uncontrolled studies, case reports and adverse-event notifications, so the evidence base is descriptive rather than confirmatory. Whether repeated melanocyte stimulation alters long-term naevus behaviour remains an open question that no completed trial has resolved.
Melanotan-2 is a synthetic cyclic heptapeptide designed as a structural analogue of alpha-melanocyte-stimulating hormone, the endogenous tridecapeptide that regulates pigment production. Two modifications distinguish it from the natural hormone: norleucine replaces methionine at the N-terminus, which limits oxidation, and a D-phenylalanine substitution raises receptor affinity. The ring is closed through an aspartate-lysine lactam bridge, giving the molecule a constrained conformation. The free base has a molecular mass near 1024 daltons, and commercial material is usually supplied as an acetate salt. It appears in the literature as a research peptide rather than an approved therapeutic agent.
Receptor studies place melanotan-2 among non-selective melanocortin agonists, binding MC1R, MC3R, MC4R and MC5R rather than a single subtype. Activation of MC1R on cutaneous melanocytes raises tyrosinase activity and shifts pigment synthesis toward eumelanin, which is darker and more photostable than pheomelanin. Central receptors, particularly MC4R, are associated with appetite suppression and with reported effects on sexual function. Because subtype selectivity is low, the same molecule engages pigment, metabolic and vascular pathways at once, and this breadth is a common explanation offered for the range of adverse events described in user reports.
Two structural changes distinguish the synthetic peptide from the natural hormone. A norleucine residue replaces methionine at one position, and a D-configured phenylalanine replaces the natural L-form at another. Both substitutions slow enzymatic breakdown, which extends the molecule's persistence relative to the parent hormone. The lactam bridge further constrains the backbone into a stable conformation. These features are standard design strategies in peptide chemistry and are not unique to this compound; they appear across many research peptides built for improved stability.
The compound was developed in the late 1980s and early 1990s by academic researchers investigating melanocortin signaling and pigmentation. Early work explored whether synthetic analogs could reproduce effects of the natural hormone under controlled conditions. The molecule never advanced through the full regulatory pathway required for approval as a medicine. From the mid-2000s onward it appeared in unregulated consumer markets, often distributed through informal channels. That gap between research origins and commercial availability shapes how the compound is discussed today.
Melanotan II is a synthetic cyclic heptapeptide with the sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, corresponding to a molecular formula of C50H69N15O9 and a monoisotopic mass near 1024 daltons. It was designed as a structural analogue of alpha-melanocyte-stimulating hormone, a peptide hormone produced by cleavage of proopiomelanocortin. A lactam bridge between the aspartate and lysine side chains closes the ring, and the C-terminal amide removes a free carboxyl group. Both modifications increase resistance to enzymatic degradation compared with the linear parent hormone. Four substitutions distinguish it from afamelanotide, the linear analogue studied under the name melanotan I.
Receptor-binding studies classify melanotan II as a non-selective melanocortin agonist. It interacts with MC1R, MC3R, MC4R and MC5R, with reported affinities in the low nanomolar range and no strong subtype preference. Activation of MC1R on dermal melanocytes shifts pigment synthesis toward eumelanin, the dark polymer deposited in melanosomes and transferred to keratinocytes. Because the same peptide engages MC4R in the hypothalamus, it also appears in animal work on food intake and erectile response, which is why it is discussed in both pigment and metabolic research. Which receptor populations dominate after systemic exposure in humans is not fully established.
Melanotan II is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone, a naturally occurring peptide involved in pigmentation signalling. Its structure substitutes a lactam bridge between side chains to increase stability relative to the native hormone. The compound is also known by the shorthand MT-II and by several non-proprietary synonyms used in research catalogues. It is not an approved therapeutic product in any major jurisdiction; material sold under this name is typically offered as a laboratory reagent rather than as a medicine.
Activity is attributed to agonism at melanocortin receptors, particularly MC1R and MC4R. Activation of MC1R on melanocytes increases melanin synthesis, which underlies the reported tanning effect. MC4R engagement in the central nervous system is linked to appetite suppression and to effects on sexual arousal reported in early clinical studies. Those studies were small and were not designed to establish efficacy or long-term safety. Receptor selectivity among the melanocortin subtypes is not absolute, which complicates attribution of any effect to a single pathway.
Regulatory treatment varies between countries. Several national medicines agencies have classified the peptide as unapproved, and customs authorities in some jurisdictions seize shipments on that basis. A few jurisdictions channel supply through prescription-only frameworks that do not list the substance by name. Because the material circulates mainly through online vendors, composition and purity are rarely verified before sale. Surveys of unapproved peptide products have reported labels that did not match measured content in a substantial fraction of samples.
=== Neurological === Although the dermatological changes are the most obvious symptoms of Urbach–Wiethe disease, many patients also have neurological symptoms. About 50–75% of the diagnosed cases of Urbach–Wiethe disease also show bilateral symmetrical calcifications on the medial temporal lobes. These calcifications often affect the amygdala and the periamygdaloid gyri. The amygdala is thought to be involved in processing biologically relevant stimuli and in emotional long-term memory, particularly those associated with fear, and both PET and MRI scans have shown a correlation between amygdala activation and episodic memory for strongly emotional stimuli. Therefore, Urbach–Wiethe disease patients with calcifications and lesions in these regions may suffer impairments in these systems. These calcifications are the result of a buildup of calcium deposits in the blood vessels within this brain region. Over time, these vessels harden and the tissue they are a part of dies, causing lesions. The amount of calcification is often related to disease duration. The true prevalence of these calcifications is difficult to accurately state as not all patients undergo brain imaging. Some patients also exhibit epilepsy and neuropsychiatric abnormalities. Epilepsy symptoms could begin with light anxiety attacks and can be controlled with anti-epileptic medications. Other patients present with symptoms similar to schizophrenia while some suffer from mood, anxiety, and psychotic disorders.
== Side effects == Nicotinamide has minimal side effects. Acute liver toxicity has been documented in at least one case with doses over 3000mg, with recommended maximum intake in non liver-impaired individuals being 1500mg. Normal doses are safe during pregnancy. Nicotinamide is contraindicated in individuals diagnosed with liver disease, and/or may cause possible drug interactions.
=== Primary === The development of osteoarthritis is correlated with a history of previous joint injury and with obesity, especially with respect to the hips and knees. Osteoarthritis of the hips and knees is twice as common in those with obesity. Changes in sex hormone levels may play a role in the development of osteoarthritis, as it is more prevalent among post-menopausal women than among men of the same age. Women also tend to have more severe symptoms and imaging findings for hip and knee osteoarthritis as compared to men. Conflicting evidence exists for the differences in hip and knee osteoarthritis in African Americans and Caucasians.
Hamburger, Cheeseburger, Double Cheeseburger, Triple Cheeseburger Big Hit (Big Mac) and Double Big Hit Grand Burger (Quarter Pounder with Cheese / McRoyal), Double Grand Burger, Grand Deluxe Burger (Quarter Pounder with Cheese Deluxe), Grand Deluxe jalapeño Big Special (Big Tasty), Double Big Special, Big Special Junior, Big Special with Mushrooms and Big Chicken Burger (Big Tasty Chicken) Fishburger (Filet-O-Fish) and Double Fishburger Chickenburger (Junior Chicken), Chicken Hit (McChicken), Chicken Hit, Chicken Premier (Seriously Chicken) and Chicken Premier with Mushrooms Caesar Roll (McWrap), Big Special Roll, Shrimp Roll, Fresh Roll and Chicken Fresh Roll French Fries / Grand Fries, Potato wedges and Potato slices Chicken nuggets, chicken strips, Fish Sticks, shrimp, apple slices and carrot sticks Vegetable salad, Caesar salad and Caesar salad with shrimp Dobry Cola (Coca-Cola), Dobry Cola Zero Sugar (Coca-Cola Zero Sugar), Dobry Orange (Fanta), Dobry Lemon-Lime (Sprite), Lipton Ice Tea Lemon, Lipton Ice Tea Green, Lemonade Strawberry-Cactus, Sunrise Strawberry-Cactus, milkshake, sundae, Ice Deluxe (McFlurry), tea, coffee and juice Kids Combo (Happy Meal) Breakfast pancakes, omelet, cherry pie and mango-passion fruit pie
Sources: en.wikipedia.org
== Alcohol and beta blockers == Alcohol, more precisely ethanol, is a colorless flammable liquid that is the intoxicating agent in fermented and distilled liquors. Beta blockers are any of a group of drugs that decrease the rate and force of heart contractions and lower high blood pressure. Beta blockers help athletes in sports such as rifle shooting or archery where nervousness can harm performance, and they are only banned in these sports. Examples beta blockers are atenolol, metoprolol, nadolol, pindolol, propranolol, and timolol.
In as much as the Meiji Restoration had sought to return the Emperor to a preeminent position, efforts were made to establish a Shinto-oriented state much like it was 1,000 years earlier. Since Shinto and Buddhism had molded into a syncretic belief in the prior thousand years and Buddhism had been closely connected with the shogunate, this involved the separation of Shinto and Buddhism (shinbutsu bunri) and the associated destruction of various Buddhist temples and related violence (haibutsu kishaku). Furthermore, a new State Shinto had to be constructed for the purpose. In 1871, the Office of Shinto Worship (ja:神祇省) was established, ranking even above the Council of State in importance. The kokutai ideas of the Mito school were embraced, and the divine ancestry of the Imperial House was emphasized. The government supported Shinto teachers, a small but important move. Although the Office of Shinto Worship was demoted in 1872, by 1877 the Home Ministry controlled all Shinto shrines and certain Shinto sects were given state recognition. Shinto was released from Buddhist administration and its properties restored. Although Buddhism suffered from state sponsorship of Shinto, it had its own resurgence. Christianity also was legalized, and Confucianism remained an important ethical doctrine. Increasingly, however, Japanese thinkers identified with Western ideology and methods.
During oogenesis, cytoplasmic bridges called "ring canals" connect the forming oocyte to nurse cells. Nutrients and developmental control molecules move from the nurse cells into the oocyte. In the figure to the left, the forming oocyte can be seen to be covered by follicular support cells. After fertilization of the oocyte, the early embryo (or syncytial embryo) undergoes rapid DNA replication and 13 nuclear divisions until about 5000 to 6000 nuclei accumulate in the unseparated cytoplasm of the embryo. By the end of the eighth division, most nuclei have migrated to the surface, surrounding the yolk sac (leaving behind only a few nuclei, which will become the yolk nuclei). After the 10th division, the pole cells form at the posterior end of the embryo, segregating the germ line from the syncytium. Finally, after the 13th division, cell membranes slowly invaginate, dividing the syncytium into individual somatic cells. Once this process is completed, gastrulation starts. Nuclear division in the early Drosophila embryo happens so quickly, no proper checkpoints exist, so mistakes may be made in division of the DNA. To get around this problem, the nuclei that have made a mistake detach from their centrosomes and fall into the centre of the embryo (yolk sac), which will not form part of the fly. The gene network (transcriptional and protein interactions) governing the early development of the fruit fly embryo is one of the best understood gene networks to date, especially the patterning along the anteroposterior (AP) and dorsoventral (DV) axes (See under morphogenesis).
=== Personal information === Personally identifying information, financial information like credit card and bank account information, and medical data from medical data breaches is bought and sold, mostly in darknet markets but also in other black markets. People increase the value of the stolen data by aggregating it with publicly available data, and sell it again for a profit, increasing the damage that can be done to the people whose data was stolen.
== M == macroevolution - macromolecular system - macromolecule - macrophage colony-stimulating factor - major histocompatibility complex - Malpighi body - Malpighi layer - marine biology - maslinic acid - mass spectrometer - maturation-promoting factor - mechanoreceptor - medicine - meiosis - melting point - membrane glycoprotein - membrane protein - membrane topology - membrane transport - memory B cell - memory T cell - Mendelian inheritance - metabolic pathway - metabolism - metabotropic glutamate receptor - metalloprotein - metaphase - metazoa - methionine - micelle - Michaelis-Menten kinetics - microbe - microbiology - microevolution - microfilament - microfilament protein - microsatellite - microscope - microtiter plate - microtubule-associated protein - mineralocorticoid receptor - minisatellite - mitochondrial membrane - mitochondrion - mitogen receptor - mitosis - mitotic spindle - mixture - modern evolutionary synthesis - molar volume - mole (unit) - molecular biology - molecular chaperone - molecular dynamics - molecular engineering - molecular evolution - molecular mechanics - molecular modelling - molecular orbital - molecular phylogeny - molecular sequence data - molecule - monoamine - monoclonal antibody - monomer - monosaccharide - monosaccharide transport protein - morphogenesis - morphogenetic field - mos gene - Mössbauer spectroscopy - MRI - MSH - mu opioid receptor - mu-chain immunoglobulin - mucin - Muller's ratchet - multiresistance - muscarinic receptor - muscle - muscle protein - mutagen - mutation - myc gene - mycology - myelin basic protein - myeloma protein - myosin
Sources: en.wikipedia.org
=== Discontinued === Acamprosate controlled-release (SNC-102) – various actions [46] ALTO-202 – NMDA receptor antagonist [47] Balovaptan (RG-7314; RO-5028442; RO-5285119) – vasopressin V1 receptor antagonist [48] Brexpiprazole (Lu-AF41156; OPC-34712; Rexulti) – atypical antipsychotic (non-selective monoamine receptor modulator) [49] Carvedilol (Coreg) – α1-, β1-, and β2-adrenergic receptor antagonist and dual alpha/beta blocker [50] Crinecerfont (Crenessity; NBI-74788; SSR-125543) – corticotropin releasing factor receptor 1 (CRF1R) antagonist [51] ENX-105 – dopamine D2 and D3 receptor agonist, dopamine D4 receptor agonist, and serotonin 5-HT1A and 5-HT2A receptor agonist [52] Fluoxetine (Prozac, Sarafem) – selective serotonin reuptake inhibitor [53] Ganaxolone (GNX; CCD-1042; Ztalmy) – GABAA receptor positive allosteric modulator and neurosteroid [54] JZP-150 (PF-04457845; PF-4457845; PF-’845) – fatty acid amide hydrolase (FAAH) inhibitor [55] Nabiximols (tetrahydrocannabinol/cannabidiol; THC/CBD; GW-1000; JZP-378; Nabidiolex®/Tetranabinex®; Sativex) – cannabinoid receptor modulator, other actions [56] Naloxone/tianeptine (TNX-601) – combination of tianeptine (weak and atypical μ-opioid receptor agonist) and naloxone (orally inactive opioid receptor antagonist) Nepicastat (APL-1401; SYN-117) – dopamine β-hydroxylase (DBH) inhibitor [57] NYX-783 – NMDA receptor modulator [58] Orvepitant (GW-823296, GW823296X) – neurokinin NK1 receptor antagonist [59] Pomaglumetad methionil (DB103; LY-2140023; LY-2812223; LY-404039 prodrug) – metabotropic glutamate mGlu2 and mGlu3 receptor agonist (pomaglumetad prodrug) [60] PRAX-114 – GABA modulator [61] PRX-3140 (PRX-03140; NTC-942) – serotonin 5-HT4 receptor agonist [62] Verucerfont (GSK-561679; NBI-77860) – corticotropin releasing factor receptor 1 (CRF1R) antagonist [63]
Axelopran is an oral PAMORA which is under development by Theravane Biopharma. It has completed phase II in clinical trials in more than 400 patients with OIC. Axelopran has a different chemical structure from other PAMORAs but with a similar mechanism of action. It acts as an antagonist for MOR, KOR and DOR, but with higher affinity for MOR and KOR than for DOR. Like other PAMORAs, the main goal is the treatment of OIC. Axelopran is also being investigated in fixed-dose combination (FDC) with oxycodone. It is done by using spray coating technology to create an FDC of axelopran and controlled-release oxycodone. There is a demand for optimization of the receptor selectivity and affinity accompanied by an exploration of candidate compounds regarding their route of administration. These are the main objectives and future strategies for drug discovery and the development of PAMORAs. Predominantly, the MORs exhibit functionally selective agonism. Therefore, future possible candidate compounds that target OIC are PAMORAs with optimized selectivity and affinity.
=== Media === In France, the French syndicate of non-alcoholic beverages "Boissons Rafraîchissantes de France" (that included soft drink producers such as Coca-Cola France, Orangina, PepsiCo France) was denounced by the French journal fr:Canard Enchainé for misleading consumers using a communication on their website titled "Better understanding the NASH pathology", explaining that "NASH pathology is sometimes called the soda illness by language abuse or an unfortunate semantic shortcut, as it is not directly linked to the consumption of non-alcoholic beverages". This page and others on the same website, such as one titled "Say no to disinformation," were removed since then.
In 1960, the Grace Line, inspired by the pioneering efforts of Sea-Land Service, Matson Navigation, and Seatrain Lines, sought to begin containerizing its South American cargo operations by converting the conventional freighters Santa Eliana and Santa Leonor into fully cellular container ships. The effort was stymied by the opposition of longshoremen in New York and Venezuela, and the ships were repeatedly laid up idle and were ultimately sold to the domestic container line Sea-Land Service in 1964. In 1963 Grace made a second attempt to containerize its South American trade when it ordered the four M-class combination passenger-cargo ships Santa Magdalaena, Santa Maria, Santa Mariana, and Santa Mercedes with partial cellular holds, but they were no more successful as mixing conventional break-bulk cargo and containers in the same ship negated the operating economies that full containerization promised. In 1970, Grace Line was sold to Prudential Lines for $44.5 million, with the merged company renamed Prudential Grace Line. It was taken over by Delta Steamship Lines in 1978, thereby extinguishing the name Grace in ocean shipping. Subsequently, Delta Steamship Lines was acquired and consolidated by Crowley Maritime in 1982.
Sources: en.wikipedia.org
No. It is a laboratory-made peptide, while the natural hormone is alpha-melanocyte-stimulating hormone, a longer peptide produced by the pituitary gland and by skin cells. Melanotan-2 mimics only a short active region of that hormone and contains non-natural residues such as D-phenylalanine.
No approved regulatory indication exists in major markets. An approval exists for a different peptide, afamelanotide, which is used for a rare photosensitivity disorder called erythropoietic protoporphyria. Melanotan-2 itself remains a research compound with no cleared clinical role.
Melanocortin-1 receptors on melanocytes are the receptor most closely linked to pigment production. The peptide is not selective, however, and also activates melanocortin-3, melanocortin-4, and melanocortin-5 receptors. That lack of selectivity is the usual explanation offered for both its range of observed effects and its off-target effects.
No regulator in a major market has approved it for human use. It appears in research settings and in products marketed outside pharmacy channels. Legal status for personal possession varies by country.