Source comparison
Melanotan-1 vs Melanotan-2: Receptor Selectivity and Side Effect Profiles
The structural difference between MT-1 and MT-2 is a single disulfide bridge. Melanotan-2 cyclizes between positions 4 and 10 (Cys-Cys bond), creating a constrained ring structure that increases potency at all five melanocortin receptors but eliminates selecti
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- The structural difference between MT-1 and MT-2 is a single disulfide bridge. Melanotan-2 cyclizes between positions 4 and 10 (Cys-Cys bond), creating a constrained ring structure that increases potency at all five melanocortin receptors but eliminates selectivity. MT-2 binds MC1R, MC3R, MC4R, and MC5R with roughly equal affinity, producing pigmentation alongside appetite suppression, increased libido, spontaneous erections, and in some cases nausea or flushing severe enough to discontinue use.
- MT-1 remains linear, preserving MC1R selectivity and avoiding off-target activation. This is why afamelanotide (pharmaceutical MT-1) received FDA approval while MT-2 remains a research compound. The side effect profile is dramatically different: Phase III trials of afamelanotide reported nausea in fewer than 5% of subjects and no sexual or appetite effects. MT-2 studies consistently report nausea in 30–50% during the loading phase and sexual effects in 60–80%.
- Structure
- Linear 13-mer peptide
- Cyclic peptide with Cys4-Cys10 bond
- MT-1 structure prevents MC4R binding
- Receptor Selectivity
- MC1R-selective (140-fold vs MC4R)
- Non-selective (binds MC1R/3R/4R/5R equally)
- MT-1 selectivity eliminates appetite and sexual effects
- Pigmentation Onset
- 3–7 days at 0.5–1.0mg/day
- 2–5 days at 0.25–0.5mg/day
- MT-2 faster but not proportionally safer
- Nausea Incidence
- <5% (Phase III data)
- 30–50% (observational data)
- MT-1 significantly better tolerated
- Sexual Side Effects
- None documented in clinical trials
- Spontaneous erections in 60–80% of male subjects
- MT-1 lacks MC4R activation
- FDA Status
- Approved (Scenesse, 2019) for EPP
- Not approved; research use only
- Only MT-1 has completed regulatory review
- The take-home: MT-1 is the version designed for therapeutic use. MT-2 was developed to enhance potency but sacrificed selectivity. If the goal is pigmentation without systemic melanocortin effects, MT-1 is mechanistically superior.