Melanotan 1 SPECIFICATIONS
Molecular Formula: C78H111N21O19
Molecular Weight: 1646.8 g/mol
PubChem: CID 16154396
CAS Number: 75921-69-6
What is Melanotan 1 peptide?
Melanotan 1 (MT-1) is a synthetic equivalent of alpha-melanocyte-stimulating hormone (alpha-MSH). In Europe, the peptide is clinically administered on patients suffering from erythropoietic protoporphyria to prevent phototoxicity or sun-related damage of the skin. It was initially formulated to act as a sunless tanning agent. Interestingly, it was also observed to influence diverse physiological processes like feeding patterns, central nervous system operations, blood pressure, and so on. The clinical trials involving the molecule are currently in phase II stage for keratosis (a particular kind of skin damage induced by sun) and the more severe squamous cell carcinoma and in phase III stage for the treatment of polymorphous light eruption.
How Does MT-1 Work?
Melanotan 1 is structurally and functionally similar to the physiological alpha melanocyte stimulating hormone (alpha-MSH). Alpha-MSH is primarily known to affect melanocytes, skin cells and hair cells that are responsible for pigmentation. The hormone interacts strongly with melanocortin receptor 1 thus mediating its role. Alpha-MSH is a non-selective agonist of melanocortin receptors 1, 3, 4, and 5 and completely stimulate them.
MT-1 varies from alpha-MSH by single amino acid and was initially developed as a sunless tanning agent. It was soon discovered that MT-1 also induces sexual arousal, boosts appetite, and modifies baseline metabolism apart from affecting skin pigmentation. Subsequent research on the peptide and other melanocortin-binding proteins helped scientists to explore the melanocortin signaling system better.
Melanotan 1 Peptide Research
Originally Designed for Sunless Tanning
MT-1 has been studied in phase I clinical trials for its tanning effect in humans exposed to ultraviolet radiation. The work showed that volunteers who were administered MT-1 showed 75% more tanning and about 47% less sunburn. Melanotan 1 induced similar tanning in subjects as compared to controls even with 50% less ultraviolet light exposure. The tan persisted on these subjects for three weeks longer than those exposed only to UV light. Hence MT-1 can be used for tanning of skin under conditions of high UV exposure thereby protecting from skin damage as well as melanomas. This would thus be an effective solution for individuals who possess skin types with poor tanning (referred to as type I and type II as per the Fitzpatrick scale).
Variant MC1 receptors in individuals cause less tanning of skin as compared to an individual with wild-type MC1 receptors. In this genetic backdrop, use MT-1 increases melanin density, induces substantial tanning and mediates photoprotection. Sunscreen is of limited use for such individuals. Hence they require to reduce their sun exposure to a significant extent to prevent skin cancer. MT-1 is thus a good alternative for UV protection and decrease frequency of skin cancer.
MT-1 is also studied to treat vitiligo. A small phase I trial showed that combinatorial use of the peptide with UVB light therapy promotes both syntheses of melanin and proliferation of melanocytes. About 50 % of the MT-1 treated vitiligo patients showed rapid repigmentation and a decrease of vitiligo patches on the skin. MT-1 may be considered to treat hypopigmented scars based on the outcome of vitiligo trial study.
Overexposure to UV light causes scaly and crusty skin growth known as actinic or solar keratosis. This precancerous lesion if left unattended can develop into squamous cell carcinoma. There are greater than 400,000 such cases every year. Unlike obvious lesions which can be surgically corrected, the small and rather invisible ones can be treated with MT-1 to prevent formation of skin cancer.
Cognitive Decline, Alzheimer’s Disease
MT-1 administration protects transgenic mice brains from cognitive decline and onset of Alzheimer’s disease (AD). Even minute amounts of the peptide have shown to decrease amyloid-beta plaques and neuronal apoptosis in brains of mice suffering from moderate AD. This enhances clinically defined cognitive function and synaptic transmission in the MT-1 treated animals. In the same study, inhibiting the effects of MT-1 at the MC4 receptor prevented all of the peptide’s favorable effects.
MC4 receptor stimulation leads to neurogenesis and recovery of cognitive function in murine models of AD. All AD-linked biomarkers decrease significantly even with a once-daily dose of the peptide. Thus the drug acts through multiple pathways.
MC4 receptor is the sole melanocortin receptor to be expressed on astrocytes, the feeder cells which help to protect and provide nutrition to neurons.MT-1 enhances production of brain-derived neurotrophic factor (BDNF) and thus stimulates astrocyte functioning. BDNF is also crucial to maintain the stability of synapse and general neurogenesis.
MMT-1 Research and Blood Pressure
MT-1 selectively helps to control hypertension in murine models without affecting animals with normal blood pressure. This role of MT-1 holds value as existing medication often leads to hypotension, heart attack, stroke and other serious manifestations. The blood pressure medicines cause more harm in elderly patients due to their age-related frail physiology. Thereby, MT-1 ability to control hypertension without triggering critically low blood pressure makes it a suitable candidate for new drug development.
Melanotan 1 and Functional Recovery Following Stroke
MT-1 helps to ameliorate adverse conditions of stroke as well. Studies on gerbil model have shown that when the peptide is used even 9 hours after stroke can help in controlling brain damage, neuronal death, and improve learning and memory. MT-1 helps the brain to reroute learning and memory to the healthier parts. Thus it helps to repair synaptic plasticity and long-term functional recovery of the brain. The most important mediator in this process is the expression of Zif268 gene. Zif268 is over-expressed in animals administered with melanotan-1. It is also overexpressed in models of AD which exhibits improvement in cognitive abilities.
Melanotan 1 Research 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 can be effectively reversed through use of MT-1. In fact, administration of MT-1 to these mice augmented myelin recovery and promoted neuron signaling.
Uveitis is another inflammatory disorder of the eye which causes pain and leads to vision loss. Melanotan 1 serves as a good alternative to the existing steroids and other immunosuppressive drugs used to treat the condition. The peptide mimics the role of alpha-MSH which suppresses T-cell function through MC4 receptors. Local administration of the MC4 agonists directly to the eye has also proven to be effective and helps to avoid the adverse effects of systemic application.
MT-1 Influences Heart and Circulation
Studies in rats have revealed the efficacy of using MT-1 and other melanocortins in reducing cardiac injury and improving circulatory parameters. Use of MT-1 during CPR and in combination with epinephrine helps to reinstate baseline arterial pressure and cardiac rate, reverses metabolic acidosis, suppresses inflammatory markers, and promotes the expression of genes associated with cardiac function. Overall, the therapy helped to increase survival rate by 81%, which proves the efficacy of using Melanotan-1 or a similar melanocortin in a cardiac emergency.
MT-1 Investigated in Fat Loss Trials
MT-1 works on MC5 receptor just like several melanocortin receptors. This interaction stimulates MC5R into lipid metabolism by muscle cells and shifts the dynamics from fat storage to fat burning. These studies in murine models prove that lipid metabolism is a complex physiological process and involves various pathways. MT-1 acts as a useful molecule to study fatty acid metabolism and means to alter the baseline physiology without the need for exercise. This can prove to be useful for individuals who cannot exercise due to injury, morbid obesity, or disability. At present, its availability at Biotech Peptides is restricted only for academic and research use and not for clinical human administration.
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