Side-by-side · Research reference

Melanotan-IIvsMK-677

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 2Reviewed13/45 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

MK-677

Oral GHS · Ibutamoren

10–25 mgDaily dose (oral)Nass 2008

Phase 2Evidence levelMurphy 1998 Nass 2008

~24 hrHalf-lifeNass 2008

Oral capsule · 1×/day

01Mechanism of Action

Parameter

Melanotan-II

MK-677

Primary target

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

Ghrelin receptor (GHS-R1a)Murphy 1998

Pathway

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

GHS-R1a → Gαq → Ca²⁺ → sustained GH pulses across 24 hrNass 2008

Downstream effect

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

Sustained GH + IGF-1 elevation; appetite stimulation; lean mass preservationNass 2008

Feedback intact?

—

Pulsatile pattern preserved despite long half-lifeMurphy 1998

Origin

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

Non-peptide spiroindane-piperidine small molecule designed at MerckMurphy 1998

Antibody development

—

02Dosage Protocols

Parameter

Melanotan-II

MK-677

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, oral

Lower / starter dose

0.1 mg / day

Conservative starter — assess tolerability for nausea.

5 mg / day

Evidence basis

Phase 1 + anecdotalDorr 1996

Phase 2 trials (Nass 2008, Murphy 1998)Nass 2008 Murphy 1998

Duration

8–12 weeks per cycle

8–16 weeks per cycle (off-cycle to reset receptor sensitivity)

Reconstitution

Bacteriostatic water; protect from light

Oral, no reconstitution

Timing

Evening preferred (24h tan-development cycle)

Pre-sleep preferred for natural GH pulse alignment

Half-life

~1 hour plasma; effects on melanocytes persist days

~24 hrNass 2008

Once-daily dosing covers 24 hours.

Standard dose

—

10–25 mg / day oralNass 2008

25 mg used in Nass 2008 elderly trial; 10–15 mg common community dose.

04Side Effects & Safety

Parameter

Melanotan-II

MK-677

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

Increased appetite

—

Strong appetite increase via ghrelin agonism

Water retention

—

Mild edema, paresthesias

Glucose tolerance

—

↑ HbA1c +0.3–0.5% in 2-yr elderly trialNass 2008

IGF-1 elevation

—

+50–100% sustainedNass 2008

Cancer risk

—

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

Cardiovascular

—

No clear adverse signal in trials; congestive heart failure caution

Drowsiness

—

Common, especially during initial weeks

Absolute Contraindications

Melanotan-II

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

MK-677

·Active malignancy
·Pregnancy / breastfeeding
·Disrupted hypothalamic-pituitary axis
·Congestive heart failure (caution)

Relative Contraindications

Melanotan-II

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

MK-677

·Untreated diabetes
·Pre-diabetes
·Severe insulin resistance

05Administration Protocol

Parameter

Melanotan-II

MK-677

1. Reconstitution

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

Capsule or oral solution. No injection.

2. Injection site

SQ — abdomen. Rotate sites.

Oral. Take with or without food.

3. Timing

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

Pre-sleep preferred — aligns with natural GH pulse.

4. Storage

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

Capsule: room temp ≤25 °C, dry place.

5. Needle

29–31G insulin syringe.

Monitor HbA1c every 8–12 weeks during chronic use.