Melanotan II (MT2)

Melanotan 2 Peptide

Melanotan 2 (MT-II) is a synthetic analog of α-melanocyte-stimulating hormone. The peptide is a cyclic heptapeptide that appears to have a modified affinity for several of the same receptors as the endogenous hormone. In addition to potentially stimulating melanogenesis (melanin production) in skin cells, MT-II may also show affinity for receptors involved in appetite regulation and certain arousal pathways.

Overview

Melanotan 2 is often described as a non-selective agonist with the potential to bind four of the five melanocortin receptor subtypes (MC-R). Depending on localization, the MT-II–receptor interaction may lead to different actions. The four receptors MT-II may engage include:

MC1R — expressed on melanocytes in dermal tissues, hair, and some ocular cells.

MC3R — found across multiple tissues, including brain and placenta; preliminarily linked to appetite modulation under certain conditions.

MC4R — localized in the central nervous system, including the hypothalamus; early reports connect it to neurons influencing mating behaviors and general arousal.

MC5R — distributed across several peripheral tissues; its precise role remains less clear.

For example, the interaction between Melanotan 2 and MC1R may increase eumelanin production, resulting in darker epidermal pigmentation.

On the other hand, when Melanotan 2 binds MC4R, it may engage supraspinal centers in the brain, which may lead to increased libido. These signals may then be carried to sympathetic and parasympathetic centers in the spinal cord and thoracolumbar region.

Chemical Makeup

Other Known Titles: MT-II
Molecular Weight: 1024.19 g/mol
Molecular Formula: C₅₀H₆₉N₁₅O₉

Research and Clinical Studies

Melanotan 2 Peptide and Nerve Cell Regeneration

Research in a murine model of induced peripheral nerve injury has been used to explore the neurotrophic potential of Melanotan 2. Within about 48 hours of peptide presentation, treated subjects showed signs of sensory recovery. When a chemotherapeutic agent was introduced, Melanotan 2 also appeared to provide partial neuroprotection against drug-induced neurotoxicity. These effects are proposed to involve MC4 receptors and may support neurite outgrowth and the intrinsic capacity of neural tissue to recover after injury.

Although the exact signaling pathways are not fully defined, POMC-derived melanocortin peptides (including α-MSH analogs) are often discussed for their ability to increase neurite number and length and to encourage sprouting in damaged regions. As a potent melanocortin receptor agonist, Melanotan 2 may trigger intracellular events that help nerve fibers regenerate after various insults and offer some protection in toxic neuropathic conditions.

Melanotan 2 Peptide and Arousal Neurosignaling

A clinical study reported increased arousal-related neuronal signaling in more than 80% of cases with Melanotan 2, compared with about 20% on placebo. The peptide is thought to act through MC4 receptors and downstream of established neuromodulators such as dopamine and oxytocin, integrating signals within hypothalamic centers that coordinate homeostatic and motivational behaviors. Some authors also suggest possible involvement of MC5 receptors in certain peripheral glands, which could provide a parallel link between central signaling and peripheral modulatory factors; mechanisms remain hypothetical.

Melanotan 2 Peptide and Neurodevelopmental Modulation

Melanotan 2 has been proposed to influence atypical neural mechanisms by stimulating neuron populations that govern aspects of social cognition via endogenous oxytocinergic signaling. MC4R-sensitive circuits—described in regions such as the paraventricular nucleus—may release oxytocin in response to Melanotan 2, potentially recalibrating imbalances in neurochemistry that involve serotonin, glutamate, dopamine, and GABA. By engaging these pathways, Melanotan 2 may alter functional connectivity across cortical and subcortical networks (for example, the anterior cingulate cortex), helping to adjust synaptic communication and plasticity.

Melanotan 2 Peptide and Models of Sunless Tanning

Melanotan 2 may boost melanin production and deepen pigmentation without ultraviolet exposure by activating MC1R on melanocytes. Its cyclic design is also described as providing longer-lasting receptor activity than some other MSH analogs.

Although the precise intracellular pathways are not fully mapped, current data indicate that these receptor interactions can elevate eumelanin synthesis. This offers a potential route for developing sunless tanning models under controlled research conditions. Reports from experimental work note increased (darkened) pigmentation on the face, upper body, and buttock.

Melanotan 2 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering.

References:

1. Ryakhovsky, Vladimir V et al. “The first preparative solution phase synthesis of Melanotan II.” Beilstein Journal of Organic Chemistry vol. 4 (2008): 39. doi:10.3762/bjoc.4.39. https://pubmed.ncbi.nlm.nih.gov/19043625/
2. Mac E. Hadley, Discovery that a melanocortin regulates sexual functions in male and female humans, Peptides, Volume 26, Issue 10, 2005, Pages 1687-1689, ISSN 0196-9781, https://doi.org/10.1016/j.peptides.2005.01.023
3. King, Stephen H et al. “Melanocortin receptors, melanotropic peptides and penile erection.” Current topics in medicinal chemistry vol. 7,11 (2007): 1098-1106. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694735/
4. Peters, Björn, et al. “Melanotan II: a possible cause of renal infarction: review of the literature and case report.” CEN case reports vol. 9,2 (2020): 159-161. doi:10.1007/s13730-020-00447-z. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148395/
5. Ter Laak, Mariël P, et al. “The potent melanocortin receptor agonist melanotan-II promotes peripheral nerve regeneration and has neuroprotective properties in the rat.” European Journal of Pharmacology vol. 462,1-3 (2003): 179-83. doi:10.1016/s0014-2999(02)02945-x. https://pubmed.ncbi.nlm.nih.gov/12591111/
6. Wessells, H et al. “Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II.” International journal of impotence research vol. 12 Suppl 4 (2000): S74-9. doi:10.1038/sj.ijir.3900582. https://pubmed.ncbi.nlm.nih.gov/11035391/
7. Minakova E, Lang J, Medel-Matus JS, Gould GG, Reynolds A, Shin D, Mazarati A, Sankar R. Melanotan-II reverses autistic features in a maternal immune activation mouse model of autism. PLoS One. 2019 Jan 10;14(1):e0210389. Doi: 10.1371/journal.pone.0210389. PMID: 30629642; PMCID: PMC6328175.
8. Dorr RT, Lines R, Levine N, Brooks C, Xiang L, Hruby VJ, Hadley ME. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci. 1996;58(20):1777-84. doi: 10.1016/0024-3205(96)00160-9. PMID: 8637402.

Dr. Marinov

Dr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.