Side-by-side · Research reference

Melanotan-IIvsSermorelin

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

APhase 1Reviewed9/43 cited

BPhase 3Reviewed14/43 cited

Melanotan-II

MC1R + MC4R agonist · Tanning + sexual response

0.25–1.0 mgPer doseDorr 1996

Phase 1Evidence levelDorr 1996

~1 hrHalf-life

SQ · Abdomen · Loading 5–7 days, then maintenance

Sermorelin

GHRH 1-29 fragment · Short-acting

100–500 mcgPer doseMolteno 2013

Phase 3Evidence levelWalker 1994 Molteno 2013

~12 minHalf-lifeMolteno 2013

SQ · Pre-sleep · 1×/day

01Mechanism of Action

Parameter

Melanotan-II

Sermorelin

Primary target

MC1R (skin) + MC3R + MC4R (CNS sexual / appetite)Dorr 1996

Pituitary GHRH receptorWalker 1994

Pathway

MC1R agonism → melanocyte tyrosinase → eumelanin synthesis. MC4R → autonomic sexual arousal centresDorr 1996 Simerly 2023

GHRH-R → Gαs → cAMP → PKA → GH vesicle exocytosisWalker 1994

Downstream effect

Skin darkening, photo-protection, increased sexual desire / spontaneous erectionDorr 1996

Pulsatile GH release; subsequent IGF-1 elevationMolteno 2013

Feedback intact?

—

Yes — short pulse preserves feedback

Origin

Cyclic 7-AA modified α-MSH analog; designed at University of ArizonaDorr 1996

Unmodified active 29-AA fragment of human GHRH (1-44)Walker 1994

Antibody development

—

02Dosage Protocols

Parameter

Melanotan-II

Sermorelin

Loading phase

0.25–0.5 mg/day SQ × 5–7 daysDorr 1996

Builds up to visible tan.

—

Maintenance

0.5–1.0 mg 1–2×/week

After visible tan develops; supports with UV exposure.

—

Frequency

Daily during loading; 1–2× per week maintenance

Once daily, pre-sleep

Lower / starter dose

0.1 mg / day

Conservative starter — assess tolerability for nausea.

100 mcg per dose

Evidence basis

Phase 1 + anecdotalDorr 1996

Phase 3 (Geref pediatric); clinical practiceWalker 1994 Molteno 2013

Duration

8–12 weeks per cycle

Reconstitution

Bacteriostatic water; protect from light

Bacteriostatic water

Timing

Evening preferred (24h tan-development cycle)

Pre-sleep, fasted preferred

Half-life

~1 hour plasma; effects on melanocytes persist days

~12 min (plasma)Molteno 2013

Shorter than tesamorelin (~26 min) — simpler GHRH analogue.

Standard dose

—

100–500 mcg per injectionMolteno 2013

04Side Effects & Safety

Parameter

Melanotan-II

Sermorelin

Nausea

Common, especially loading phase

—

Flushing

Common transient

—

Spontaneous erection

Common in men — MC4R cross-effectDorr 1996

—

Increased mole / freckle pigmentation

Existing moles darken; new lesions possible

—

Melanoma risk

Theoretical concern — increased melanocyte activity; CAUTION in melanoma history

—

Appetite suppression

MC4R-mediated; mild

—

Pregnancy / OB

Contraindicated

Avoid

Injection site reaction

—

Mild erythema, transient pain

Flushing / headache

—

Common transient effect

IGF-1 elevation

—

Modest at standard doses

Cancer risk

—

Contraindicated in active malignancy (GH/IGF-1 axis)

Glucose handling

—

Generally neutral

Absolute Contraindications

Melanotan-II

·History of melanoma or atypical mole syndrome
·Pregnancy / breastfeeding
·Active uncontrolled hypertension

Sermorelin

·Active malignancy
·Pregnancy / breastfeeding
·Disrupted hypothalamic-pituitary axis

Relative Contraindications

Melanotan-II

·Significant freckling / dysplastic nevus
·Personal or family melanoma history

Sermorelin

·Untreated diabetes

05Administration Protocol

Parameter

Melanotan-II

Sermorelin

1. Reconstitution

Add 2 mL bacteriostatic water to 10 mg vial → 5 mg/mL = 500 mcg per 0.1 mL. Light-protected.

Add 2 mL bacteriostatic water to 5 mg vial → 2.5 mg/mL = 250 mcg per 0.1 mL.

2. Injection site

SQ — abdomen. Rotate sites.

SQ — abdomen or thigh. Rotate sites.

3. Timing

Evening preferred. UV exposure (sunlight or tanning bed) helps develop tan.

Pre-sleep, fasted.

4. Storage

Lyophilised: refrigerate, light-protected. Reconstituted: refrigerate ≤30 days.

Lyophilised: room temp, light-protected. Reconstituted: refrigerate ≤30 days.

5. Needle

29–31G insulin syringe.

29–31G, 4–8 mm insulin syringe.

06Stack Synergy

Melanotan-II

— no documented stacks

Sermorelin

+ Ipamorelin

Strong

View Ipamorelin →

Sermorelin (GHRH analogue) and ipamorelin (selective GHRP) form the prototypical GHRH+GHRP dual-axis stack at the lowest cost. Both peak within 30 min and produce a sharp physiological GH pulse without cortisol/prolactin elevation.

Sermorelin: 200–300 mcg SQ · pre-sleep
Ipamorelin: 200–300 mcg SQ · same injection
Primary benefit: Pulsatile GH stimulation, recovery, body composition

Raun 1998 Walker 1994