Melanotan 1 & 2: Melanocortin Peptide Research Guide

Melanotan 1 (MT1/Afamelanotide) and Melanotan 2 (MT2) are synthetic analogs of alpha-melanocyte-stimulating hormone (α-MSH) with distinct structural properties, receptor selectivity, and research applications. - Structure: Linear peptide, 13 amino acids - Sequence: Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂ - Molecular Weight: 1,646 Da - Key modifications: Norleucine at position 4, D-phenylalanine at position 7 - Structure: Cyclic heptapeptide, 7 amino acids - Sequence: Ac-Nle-cycloAsp-His-D-Phe-Arg-Trp-Lys-NH₂ - Molecular Weight: 1,024 Da - Key modification: Lactam bridge between Asp and Lys | Receptor | Melanotan 1 | Melanotan 2 | Primary Function | |----------|-------------|-------------|------------------| | MC1R | +++++ (High) | ++++ (High) | Pigmentation | | MC2R | + (Minimal) | + (Minimal) | ACTH/cortisol | | MC3R | + (Low) | +++ (Moderate) | Energy homeostasis | | MC4R | + (Low) | +++++ (Very High) | Sexual function, appetite | | MC5R | ++ (Moderate) | +++ (Moderate) | Exocrine function | Key Difference: Melanotan 1 is a selective MC1R agonist, while Melanotan 2 is a non-selective multi-receptor agonist. 1. Binds MC1R on melanocytes 2. Activates adenylyl cyclase → increases cAMP 3. Stimulates tyrosinase enzyme 4. Increases eumelanin (protective pigment) synthesis 1. MC1R: Pigmentation (similar to MT1) 2. MC3R: Energy homeostasis, metabolism regulation 3. MC4R: Sexual arousal, erectile function, appetite suppression 4. MC5R: Exocrine gland function | Parameter | Melanotan 1 | Melanotan 2 | |-----------|-------------|-------------| | Onset | Slower, gradual | Faster, rapid | | Potency | Moderate | Superpotent | | Duration | Weeks to months | Shorter cycles | | Pigmentation increase | 75% | Higher at lower doses | | Sunburn risk reduction | 47% | Similar | - Enhanced libido and erectile function - Appetite suppression (anorexigenic effect) - Central nervous system arousal - Led to development of PT-141/Bremelanotide (FDA-approved for HSDD) | Compound | Status | Indication | |----------|--------|------------| | Melanotan 1 | FDA-approved (SCENESSE®) | Erythropoietic protoporphyria (EPP) | | Melanotan 2 | Not FDA-approved | Research compound | | PT-141/Bremelanotide | FDA-approved | Hypoactive sexual desire disorder | - MC1R-specific signaling studies - UV damage and photoprotection research - Photosensitivity disorders (EPP, polymorphic light eruption) - Predictable, focused pigmentation studies - Multi-receptor melanocortin system investigations - Sexual dysfunction research (ED, HSDD) - Appetite and metabolism studies - Structure-activity relationship studies - Autism spectrum behavior research (MC3R pathway) - Temporary redness/flushing - Mild fatigue - Light headaches - Generally well-tolerated - Nausea (more common) - Facial flushing - Appetite suppression - Increased heart rate - Spontaneous erections - Blood pressure changes | Feature | Melanotan 1 | Melanotan 2 | |---------|