Melanotan II vs MOTS-c

Mechanism

Melanotan II is a synthetic cyclic analog of alpha-melanocyte-stimulating hormone (alpha-MSH) that non-selectively agonizes melanocortin receptors MC1, MC3, MC4, and MC5. MC1R activation stimulates eumelanin synthesis through tyrosinase upregulation, producing tanning. MC3R activation in the CNS increases libido and produces erectile responses. MC4R activation suppresses appetite. The cyclic structure provides enhanced in vivo stability (half-life 1-2 hours) and increased blood-brain barrier permeability compared to linear alpha-MSH.

Standard Dosing

Research indicates 250-500 mcg daily via subcutaneous injection during loading, reducing to 250 mcg 2-3 times weekly for maintenance.

Timing

Administer 4-6 hours before UV exposure for optimal tanning synergy. Can be taken at any time of day.

Cycle Duration

Loading phase 1-2 weeks, then maintenance as long as desired. Pigmentation fades gradually upon discontinuation.

Side Effects

• Nausea (common, especially during loading)
• Facial flushing
• Spontaneous erections
• Appetite suppression
• Darkening of existing moles (monitor closely)
• Fatigue
• New nevus formation

Contraindications

• History of melanoma or atypical moles
• Active skin cancer
• Pregnancy and breastfeeding
• Addison's disease
• Pheochromocytoma

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Mechanism

MOTS-c is a 16-amino acid mitochondrial-derived peptide encoded by the 12S rRNA gene of the mitochondrial genome. It primarily acts through the folate-AICAR-AMPK pathway: by regulating the folate cycle and de novo purine biosynthesis, it increases AICAR accumulation, which phosphorylates and activates AMPK. This enhances glucose uptake in skeletal muscle, improves insulin sensitivity, and mimics exercise-mediated physiological responses. Skeletal muscle MOTS-c levels increase 11.9-fold in response to acute exercise in young men.

Standard Dosing

Research indicates 5-10 mg administered 3-5 times per week via subcutaneous injection.

Timing

Morning administration preferred. Can be dosed pre-workout for enhanced exercise performance.

Cycle Duration

8-16 week cycles.

Side Effects

• Injection site reactions
• Mild fatigue post-injection
• Transient flushing
• Muscle soreness (exercise-mimetic effect)

Contraindications

• Pregnancy and breastfeeding
• Type 1 diabetes (insulin sensitivity changes require monitoring)
• Not FDA-approved
• Limited human safety data
• Active cancer (metabolic pathway activation)

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