Melanotan II / PT-141
aka MT-II, Bremelanotide, Vyleesi
Class Synthetic melanocortin peptide pan-agonist
Status MT-II: research chemical; PT-141: FDA approved 2019 (Vyleesi, female HSDD)
TL;DR
MT-II floods all melanocortin receptors simultaneously — tanning (MC1R), appetite suppression + thermogenesis (MC3R/4R), and central sexual arousal (MC4R) all happen at once because each receptor is doing exactly what it’s supposed to do. PT-141 (Bremelanotide) has one C-terminal change that shifts toward MC3R/4R with reduced (not eliminated) MC1R activity — FDA approved for female HSDD. Most practical stack use: (1) libido countermeasure during aggressive GLP-1 caloric restriction, (2) metabolic repartitioning via separate appetite axis from GLP-1.
Key Facts
| Mechanisms | MC1R (tanning); MC3R/MC4R (appetite + thermogenesis); MC4R (sexual arousal) |
| MC1R tanning | Shifts pheomelanin → eumelanin; 47% reduction in sunburn cells |
| MC4R erection | Central — different from PDE5i; generates desire independently of peripheral mechanics |
| Dosing (MT-II) | Loading: 0.5–1 mg/day 1–2 wks; maintenance: 0.5–1 mg every 2–3 days |
| Dosing (PT-141) | FDA approved: 1.75 mg SubQ 45 min before activity; community: 0.5–2 mg |
| Key risk | Transient BP/HR spike (MC4R sympathetic activation); nausea; mole darkening (FAMMM = contraindication) |
Melanocortin Receptors
| Receptor | Function | MT-II | PT-141 |
|---|---|---|---|
| MC1R | Pigmentation, anti-inflammatory | +++ | + |
| MC2R | Steroidogenesis (ACTH only) | — | — |
| MC3R | Energy homeostasis, anti-inflammatory | +++ | ++ |
| MC4R | Satiety, thermogenesis, erection/desire, sympathetic | +++ | +++ |
| MC5R | Exocrine, immunoregulation | + | + |
Three Effects
1. Tanning / Photoprotection (MC1R)
- Shifts red/yellow pheomelanin → dark brown/black eumelanin
- Genuine UV photoprotection: 47% reduction in sunburn cells
- Loading phase: 0.5–1 mg/day SubQ × 1–2 weeks; maintenance 1–2×/week
- Mole risk: screen before use; monitor during; FAMMM syndrome = contraindication
2. Sexual Function / Desire (MC4R)
- Different from PDE5i: Central (hypothalamic PVN) vs. peripheral vascular
- PDE5i requires baseline stimulation; MT-II/PT-141 generates desire independently
- MT-II + sildenafil: 5.3× greater erectile activity duration vs. sildenafil alone
- PT-141 FDA-approved for female HSDD (premenopausal)
3. Appetite Suppression + Thermogenesis (MC3R/MC4R)
- Separate axis from GLP-1: Direct hypothalamic suppression vs. vagal/gastric stretch signaling
- Additive when stacked with Retatrutide
- Setmelanotide (MC4R agonist): 12.6% weight loss in POMC-deficient obesity
- Even when appetite habituates: body mass/adiposity remain reduced (metabolic repartitioner, not just anorexiant)
- MT-II: >2× UCP1 upregulation in brown adipose tissue
Nausea Management
- Start low, titrate slowly — autonomic system habituates
- Night dosing (inject before sleep) — sleep through the BP/HR spike
- Antihistamines or ondansetron for refractory nausea
Key Stacks
| Stack | Rationale |
|---|---|
| + Retatrutide | MC4R appetite axis is separate from GLP-1; additive metabolic effect; counters GLP-1 libido decline |
| + BPC-157 | General tissue integrity during aggressive protocols |
| + SLU-PP-332 | Both affect metabolic rate via different mechanisms |
Links
- Peptides MOC
- GLP-1 GIP Glucagon — separate appetite axis
Source: Gemini Deep Research · FDA Vyleesi approval data · Dorr et al. tanning studies · PeptideDosages.com 2026-03-20