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

This phase I pilot study represented the first clinical evaluation in humans of Melanotan-II (MT-II), a superpotent cyclic analogue of alpha-melanocyte-stimulating hormone (α-MSH). The study involved 3 healthy male volunteers who received escalating subcutaneous doses of MT-II (0.01 to 0.025 mg/kg) over 5 days.

The most evident result was the induction of visible skin tanning even at relatively low doses, confirming that MT-II retains in humans the potent melanogenic activity observed in animal models. Pigmentation was observed in both sun-exposed and unexposed areas, indicating direct melanocyte stimulation independent of UV radiation.

An unexpected finding in the original protocol was the occurrence of spontaneous penile erections in the volunteers, an effect that led to subsequent investigations into the role of melanocortin receptors in sexual function. This side effect ultimately became one of the main research fields derived from MT-II.

Adverse events included transient nausea at higher doses, facial flushing, and mild fatigue. The pharmacokinetic profile indicated rapid subcutaneous absorption. This inaugural study paved the way for all subsequent research with melanocortin analogues, both for photoprotection and erectile dysfunction, serving as the basis for the development of bremelanotide (PT-141).