Melanotan 1 (MT-1) is a synthetic equivalent of alpha-melanocyte-stimulating hormone (alpha-MSH). The peptide has been exhaustively researched in research models of erythropoietic protoporphyria to potentially reduce phototoxicity or UV-related damage.[1] It was suggested to have the potential to influence diverse physiological processes like feeding patterns, central nervous system operations, blood pressure, etc. The molecule’s clinical trials are currently in phase II stage for keratosis. The more severe squamous cell carcinoma is in phase III stage within the context of polymorphous light eruption.
OTHER KNOWN TITLES: MT-1
MOLECULAR FORMULA: C78H111N21O19
MOLECULAR WEIGHT: 1646.8 g/mol
SEQUENCE: Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2
Melanotan 1 is structurally and functionally similar to the physiological alpha-melanocyte-stimulating hormone (alpha-MSH). Alpha-MSH is primarily considered to impact melanocytes, skin cells, and hair follicle cells responsible for pigmentation. This hormone appears to interact with melanocortin receptor 1, potentially thus mediating its role. Alpha-MSH is considered to be a non-selective agonist of melanocortin receptors 1, 3, 4, and 5. MT-1 varies from alpha-MSH by a single amino acid and was initially developed to induce melanin production and pigmentation. Subsequent research on the peptide and other melanocortin-binding proteins helped scientists to explore the melanocortin signaling system better.
MELANOTAN 1 AND MELANIN
MT-1 has been studied in phase I clinical trials for its melanin-inducing potential in research models exposed to ultraviolet radiation.[2] The work observed that models exposed to MT-1 exhibited a reported 75% increase in pigmentation and roughly 47% less burn. Melanotan 1 appeared to induce similar pigmentation in models compared to controls even with 50% less ultraviolet light exposure. The pigmentation persisted on these subjects for three weeks longer than those exposed only to UV light. Variant MC1 receptors may induce less skin pigmentation than wild-type MC1 receptors. In this genetic backdrop, the exposure of MT-1 may increase melanin density, induce substantial pigmentation, and potentially mediate photoprotection.
MT-1 is also studied in the context of Vitiligo. Studies noted that combinatorial exposure of the peptide with UVB light appeared to promote both syntheses of melanin and proliferation of melanocytes. About 50 % of the MT-1 exposed vitiligo models exhibited apparent rapid re-pigmentation and a decrease of vitiligo patching. MT-1 may impact hypopigmented scars based on the outcome of vitiligo research study. Overexposure to UV light may lead to scaly growth known as actinic or solar keratosis. This precancerous lesion has been associated with the development of squamous cell carcinoma.
MELANOTAN 1 AND COGNITIVE DECLINE, ALZHEIMER’S DISEASE
MT-1 exposure appeared to protect transgenic mice brains from cognitive decline and the onset of Alzheimer’s disease (AD).[3] The researchers suggested that the melanocortin receptor activation by MT-1 “restores the impaired homeostatic processes and microglial reactivity in the hippocampus in APP/PS1 mice.” Even minute amounts of the peptide were observed in an experimental study to decrease amyloid-beta plaques and neuronal apoptosis in the brains of mice suffering from moderate AD. This may enhance cognitive function and synaptic transmission in the MT-1 exposed animals. In the same study, inhibiting the effects of MT-1 at the MC4 receptor appeared to prevent all of the peptide’s considered favorable impacts. MC4 receptor stimulation may lead to neurogenesis and cognitive function recovery in murine AD models. All AD-linked biomarkers appeared to decrease significantly even with limited exposure to the peptide. The MC4 receptor is the sole melanocortin receptor to be expressed on astrocytes, the feeder cells that help to protect and provide nutrition to neurons. MT-1 is under study for its potential to enhance the production of brain-derived neurotrophic factor (BDNF) and may stimulate astrocyte functioning. BDNF is considered crucial to maintaining the stability of synapses and general neurogenesis.
MELANOTAN 1 AND BLOOD PRESSURE, STROKE
MT-1 appears to selectively help control hypertension in murine models without impacting control models with normal blood pressure.[4] This role of MT-1 possibly may avoid instances of hypotension, heart attack, stroke, or other serious manifestations. MT-1 appears in research to alleviate adverse conditions of stroke as well. Studies on the gerbil model have suggested that when the peptide is exposed even 9 hours after a stroke, it may help in controlling brain damage, neuronal death, and improve learning and memory.[5] MT-1 appears to assist the brain to reroute learning and memory circuits. The peptide, researchers suggest, may thereby potentially repair synaptic plasticity and long-term functional recovery of the brain. The most important mediator in this process is the expression of the Zif268 gene. Zif268 is reported to be over-expressed in animals exposed to Melanotan 1.
MELANOTAN 1 AND NEUROINFLAMMATORY DISEASE
MC1 receptor was recently observed to induce inflammation in the central nervous system in mice. T helper cells attack the myelin sheath in neurons leading to neuronal dysfunction and even death in multiple sclerosis. The damage was apparently reversed in research studies through the introduction of MT-1. In fact, the MT-1 appeared to augment myelin recovery and promoted neuron signaling.[6] Uveitis is another inflammatory disorder of the eye which is considered to lead to vision loss. Melanotan 1 may host the potential to mimic alpha-MSH’s role, which may suppress T-cell function through MC4 receptors. Local exposure of the MC4 agonists directly to the eye has also appeared to be potentially effective.[7]
MELANOTAN 1 AND HEART, CIRCULATION FUNCTIONS
Studies in rats have suggested MT-1 and other melanocortins may act in reducing cardiac injury and improving circulatory parameters. The exposure of MT-1 during CPR and in combination with epinephrine appeared to reinstate baseline arterial pressure and cardiac rate, reversing metabolic acidosis, suppressing inflammatory markers, and promoting the expression of genes associated with cardiac function. Overall, the procedure appeared to help increase the survival rate in the rat models by 81%, suggesting the efficacy of Melanotan-1 or a similar melanocortin in a cardiac instances.
MELANOTAN 1 AND FAT CELLS
MT-1 appears to work directly on the MC5 receptor, like several melanocortin receptors. This interaction appears to stimulate MC5R into lipid metabolism by muscle cells and may shift the dynamics from fat storage to fat burning. These studies in murine models put forth the theory that lipid metabolism may be a complex physiological process and may incorporate various pathways.[8] Research in mice suggests that exposure to the peptide may lead “to weight loss that affects both the visceral and subcutaneous fat compartments.” MT-1 may act as a experimental molecule to study fatty acid metabolism and the means to alter the baseline physiology.
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