Dorr · Life sciences 1996 · Single-blind placebo-controlled dose-escalation trial · n=3

Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study.

Cited 135 times in the scientific literature.

Level 3 - non-randomized controlled study

Non-randomized single-blind controlled pilot study

PubMed 8637402 · doi:10.1016/0024-3205(96)00160-9 · record verified 2026-08-27

What was done

A single-blind, placebo-controlled pilot phase I dose-escalation trial evaluated Melanotan-II (MT-II) in 3 healthy male volunteers. Participants received subcutaneous injections of MT-II or saline on alternating weekdays over 2 consecutive weeks (5 total MT-II doses). The starting dose was 0.01 mg/kg, escalating in 0.005 mg/kg increments to 0.025 mg/kg (n = 1) or 0.03 mg/kg (n = 2). Skin tanning was assessed visually and by quantitative reflectance, and adverse clinical effects were recorded.

What was found

Two subjects developed increased pigmentation on the face, upper body, and buttocks by 1 week post-treatment. Adverse effects included mild nausea across most dose levels and Grade II somnolence and fatigue in 1 of 2 subjects at the 0.03 mg/kg dose. MT-II dosing also triggered a stretching and yawning complex followed by spontaneous penile erections lasting 1 to 5 hours. The authors identified 0.025 mg/kg/day as the recommended dose for subsequent phase I testing.

Why it matters

This study provided the initial human proof-of-concept that MT-II stimulates melanogenesis at low doses and first documented its potent erectogenic side effect in men.

Limits

The sample size was tiny (n = 3) and restricted exclusively to healthy males. The trial used a single-blind, non-randomized design with very short exposure (five total active doses), precluding broader conclusions on efficacy, optimal dosing, or rare adverse effects.

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