Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II

This double-blind placebo-controlled study evaluated the effects of Melanotan II (MT-II) on erectile function and sexual motivation in 20 men diagnosed with erectile dysfunction (ED) of various etiologies (organic and psychogenic). Participants received subcutaneous MT-II or placebo in crossover sessions, with penile rigidity monitoring by RigiScan for 6 hours.

The results were remarkably positive: MT-II induced clinically significant penile erection (rigidity >60% at tip and base) in 17 of 20 participants (85%), in the absence of any visual or tactile sexual stimulus. In contrast, placebo produced an erectile response in only 3 of 20 participants.

Beyond the objective erectile effect, MT-II elicited increased subjective sexual desire in 68% of administrations versus only 19% of placebo administrations. This combination of improved erectile capacity and sexual desire is particularly relevant, as PDE5 inhibitors (such as sildenafil) act only on the mechanics of erection without affecting libido.

The mechanism of action of MT-II on sexual function involves activation of MC3R and MC4R receptors in the central nervous system, specifically in the hypothalamus and medial preoptic area, initiating the neural signal cascade leading to erection. This central mechanism fundamentally differentiates MT-II from peripheral ED treatments and motivated the development of bremelanotide (PT-141, approved as Vyleesi) for sexual dysfunction.