This is a working overview of melanocortin receptor, written for readers who want more than a one-paragraph summary but less than a textbook.
This page was last updated on 2026-03-14 and is reviewed periodically as new material appears.
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.
Melanotan-2 is a synthetic cyclic heptapeptide designed as an analogue of alpha-melanocyte-stimulating hormone, the naturally occurring peptide involved in pigmentation signalling. Its sequence is conventionally written as Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, with a lactam bridge joining the aspartate side chain to the lysine side chain. The empirical formula is C50H69N15O9 and the monoisotopic mass lies near 1023.5 daltons. N-terminal acetylation and the D-configured phenylalanine both increase resistance to enzymatic breakdown compared with the parent hormone.
Pharmacologically, melanotan-2 behaves as a non-selective agonist across the melanocortin receptor family. Binding at MC1R on dermal melanocytes promotes eumelanin synthesis, which underlies the tanning response described in early human work. Activity at the centrally expressed MC4R receptor is associated with reported effects on appetite and erectile function. Because the peptide does not discriminate strongly among receptor subtypes, attributing any single observed effect to one receptor pathway is generally not possible without selective antagonists or receptor knockout models.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C50H69N15O9 | Free base; salt forms add to total mass |
| Molecular mass | About 1024 daltons | Calculated for the free base |
| Structural class | Cyclic heptapeptide | Contains D-phenylalanine and norleucine |
| Parent hormone | Alpha-melanocyte-stimulating hormone | Endogenous tridecapeptide of 13 residues |
| Receptor profile | Non-selective melanocortin agonist | Interacts with MC1R, MC3R, MC4R and MC5R |
Melanotan-2 is a synthetic linear peptide built from seven amino acids arranged in a short chain. Its sequence is commonly written as Ac-Nle-Asp-His-D-Phe-Arg-Trp-Lys-NH2, which includes a modified N-terminus and an amidated C-terminus. The molecule belongs to the melanocortin family and acts as a receptor agonist. Structural features such as the D-phenylalanine residue and the Nle substitution are associated with increased stability against enzymatic degradation relative to the natural parent peptide.
The compound emerged from research programs in the 1980s that examined analogues of alpha-melanocyte-stimulating hormone for pigmentation and photoprotection. Investigators modified the native sequence to extend activity duration and potency. A related analogue, afamelanotide, was developed within the same broad line of inquiry and eventually gained approval in certain jurisdictions for a rare light-sensitivity condition. Melanotan-2 itself did not progress through the same regulatory route and has no approved therapeutic indication.
=== 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]
== Sources in nature == Apigenin is found in many fruits and vegetables, but parsley, celery, celeriac, and chamomile tea are the most common sources. Apigenin is particularly abundant in the flowers of chamomile plants, constituting 68% of total flavonoids. Dried parsley can contain about 45 mg apigenin per gram. The apigenin content of fresh parsley is reportedly 215 mg per 100 grams, which is much higher than the next highest food source.
==== Cultural model ==== Drawing on fieldwork with the Camba of Bolivia in the 1950s, Dwight Heath described a community in which adults drank heavily and became intoxicated at communal festivals, yet held no concept of alcoholism and showed no evident social problems attributed to drinking. Heath argued from this that the problems associated with heavy drinking are culturally determined and therefore vary between societies, challenging the assumption that sustained heavy use is inevitably addictive and harmful. The model drew criticism from the sociologist Robin Room and others, who held that anthropologists working in this tradition tended to understate the severity of alcohol problems; Merrill Singer has observed that these ethnographers belonged to a generation socialised to regard heavy drinking as normal.
Sources: en.wikipedia.org
=== Density === The alkali metals all have the same crystal structure (body-centred cubic) and thus the only relevant factors are the number of atoms that can fit into a certain volume and the mass of one of the atoms, since density is defined as mass per unit volume. The first factor depends on the volume of the atom and thus the atomic radius, which increases going down the group; thus, the volume of an alkali metal atom increases going down the group. The mass of an alkali metal atom also increases going down the group. Thus, the trend for the densities of the alkali metals depends on their atomic weights and atomic radii; if figures for these two factors are known, the ratios between the densities of the alkali metals can then be calculated. The resultant trend is that the densities of the alkali metals increase down the table, with an exception at potassium. Due to having the lowest atomic weight and the largest atomic radius of all the elements in their periods, the alkali metals are the least dense metals in the periodic table. Lithium, sodium, and potassium are the only three metals in the periodic table that are less dense than water: in fact, lithium is the least dense known solid at room temperature.
Absenta ("absinthe" in Spanish) is sometimes associated with a regional style that often differed slightly from its French cousin. Traditional absentas may taste slightly different due to their use of Alicante anise, and often exhibit a characteristic citrus flavour. Hausgemacht (German for home-made, often abbreviated as HG) refers to clandestine absinthe (not to be confused with the Swiss La Clandestine brand) that is home-distilled by hobbyists. It should not be confused with absinthe kits. Hausgemacht absinthe is produced in tiny quantities for personal use and not for the commercial market. Clandestine production increased after absinthe was banned, when small producers went underground, most notably in Switzerland. Although the ban has been lifted in Switzerland, some clandestine distillers have not legitimised their production. Authorities believe that high taxes on alcohol and the mystique of being underground are likely reasons.
== Structure == The human form of IAPP has the amino acid sequence KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY, with a disulfide bridge between cysteine residues 2 and 7. Both the amidated C-terminus and the disulfide bridge are necessary for the full biological activity of amylin. IAPP is capable of forming amyloid fibrils in vitro. Within the fibrillization reaction, the early prefibrillar structures are extremely toxic to beta-cell and insuloma cell cultures. Later amyloid fiber structures also seem to have some cytotoxic effect on cell cultures. Studies have shown that fibrils are the end product and not necessarily the most toxic form of amyloid proteins/peptides in general. A non-fibril forming peptide (1–19 residues of human amylin) is toxic like the full-length peptide but the respective segment of rat amylin is not. It was also demonstrated by solid-state NMR spectroscopy that the fragment 20-29 of the human-amylin fragments membranes. Rats and mice have six substitutions (three of which are proline substitutions at positions 25, 28 and 29) that are believed to prevent the formation of amyloid fibrils, although not completely as seen by its propensity to form amyloid fibrils in vitro. Rat IAPP is nontoxic to beta-cells when overexpressed in transgenic rodents.
Sources: en.wikipedia.org
Among mammals, species maximum lifespan varies significantly from one year in the yellow-sided opossum to 211 years in the oldest bowhead whale recorded. Although the underlying basis for these lifespan differences is still uncertain, numerous studies indicate that the ability to repair DNA damage is an important determinant of mammalian lifespan. In a 1974 study by Hart and Setlow, it was found that DNA excision repair capability increased systematically with species lifespan among seven mammalian species. Species lifespan was observed to be robustly correlated with the capacity to recognize DNA double-strand breaks as well as the level of the DNA repair protein Ku80. In a study of the cells from sixteen mammalian species, genes employed in DNA repair were found to be up-regulated in the longer-lived species. The cellular level of the DNA repair enzyme poly ADP ribose polymerase was found to correlate with species lifespan in a study of 13 mammalian species. Three additional studies of a variety of mammalian species also reported a correlation between species lifespan and DNA repair capability.
== Bibliography == Guillén, Mauro F.; García-Cana, Esteban (2010). Guillén, Mauro F.; García-Cana, Esteban (2010). The New Multinationals: Spanish Firms in a Global Context (in Spanish). Cambridge: Cambridge University Press. ISBN 9780521516143. VV.AA. (2012). Expansión (ed.). Las 40 empresas que crecen en tiempos de crisis (in Spanish). Bubok Publishing. ISBN 978-84-686-3028-1. Martínez Bernal, Pablo; Freischütz, Christian (2026). Los outsiders ibéricos. Ocho equipos directivos y el secreto de su éxito (in Spanish). Madrid: Marcial Pons. ISBN 9791399097016.
=== The Middle === Shaffer is most known for his role as Brick Heck in The Middle, which he played throughout the series' entire nine-season run, from 2009 to 2018. In a Wired magazine interview published in January 2013, Shaffer said his role as Brick was similar to his own life, as he is also a "big reader" and "nerd[s] out over the weirdest stuff". In May 2011, a TV Guide article had reported the closeness as well. Brick's characterization, including his idiosyncratic palilalian repetition of words and phrases at the end of sentences, is based on Justin Heisler, the son of The Middle co-creator Eileen Heisler.
Sources: en.wikipedia.org
No regulatory agency has authorised melanotan-2 as a medicine for any indication. It circulates mainly as a research chemical or through unregulated channels. As a result, identity, purity and content are not independently guaranteed.
Melanotan-1, also called afamelanotide, is a linear analogue with greater selectivity for MC1R and has received approval in some jurisdictions for a specific photosensitivity disorder. Melanotan-2 is cyclic, less selective, and reaches central receptors more readily. The two are often confused in online discussion despite different pharmacology and regulatory status.
Alpha-MSH is an endogenous tridecapeptide derived from pro-opiomelanocortin. Melanotan-2 reproduces its core receptor-binding sequence inside a shortened, stabilised ring. The result is a molecule with a longer effective half-life and higher potency than the parent hormone.
It is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone, containing seven amino acids with a lactam ring and a D-configured phenylalanine residue. It is supplied as a lyophilised powder for laboratory research.